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. 1993 Aug 1;178(2):497–507. doi: 10.1084/jem.178.2.497

CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation

PMCID: PMC2191099  PMID: 8340756

Abstract

The in vivo administration of certain monoclonal antibodies (mAbs) against the adhesion receptor, CD44, into normal mice induces both a modulation of CD44 from the surface of peripheral lymphocytes, and a concomitant increase in the amount of soluble CD44 in the serum. CD44- negative lymphocytes isolated from anti-CD44-treated mice exhibit normal homing patterns upon adoptive transfer, and are capable of reexpressing CD44 upon activation. The treatment of haptensensitized mice with anti-CD44 mAb inhibits their ability to mount a cutaneous delayed-type hypersensitivity (DTH) response within the first 24 h after hapten challenge. This inhibition reflects a block in both the edema and leukocyte infiltration of the cutaneous site of DTH, whereas the extravasation and accumulation of leukocytes in the draining lymph nodes progress normally. After 72 h, the leukocytes that extravasate into the site of antigen challenge express CD44. These results indicate that CD44 is not necessary for normal leukocyte circulation but is required for leukocyte extravasation into an inflammatory site involving nonlymphoid tissue.

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Selected References

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  1. Arch R., Wirth K., Hofmann M., Ponta H., Matzku S., Herrlich P., Zöller M. Participation in normal immune responses of a metastasis-inducing splice variant of CD44. Science. 1992 Jul 31;257(5070):682–685. doi: 10.1126/science.1496383. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
  3. Bazil V., Horejsí V. Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand. J Immunol. 1992 Aug 1;149(3):747–753. [PubMed] [Google Scholar]
  4. Belitsos P. C., Hildreth J. E., August J. T. Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression. J Immunol. 1990 Mar 1;144(5):1661–1670. [PubMed] [Google Scholar]
  5. Birkeland M. L., Johnson P., Trowbridge I. S., Puré E. Changes in CD45 isoform expression accompany antigen-induced murine T-cell activation. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6734–6738. doi: 10.1073/pnas.86.17.6734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown T. A., Bouchard T., St John T., Wayner E., Carter W. G. Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons. J Cell Biol. 1991 Apr;113(1):207–221. doi: 10.1083/jcb.113.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Budd R. C., Cerottini J. C., MacDonald H. R. Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. J Immunol. 1987 Jun 1;138(11):3583–3586. [PubMed] [Google Scholar]
  8. Camp R. L., Kraus T. A., Puré E. Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages. J Cell Biol. 1991 Dec;115(5):1283–1292. doi: 10.1083/jcb.115.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Campbell R. D., Love S. H., Whiteheart S. W., Young B., Myrvik Q. N. Increased hyaluronic acid is associated with dermal delayed-type hypersensitivity. Inflammation. 1982 Sep;6(3):235–244. doi: 10.1007/BF00916405. [DOI] [PubMed] [Google Scholar]
  10. Culty M., Miyake K., Kincade P. W., Sikorski E., Butcher E. C., Underhill C., Silorski E. The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins. J Cell Biol. 1990 Dec;111(6 Pt 1):2765–2774. doi: 10.1083/jcb.111.6.2765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamann A., Jablonski-Westrich D., Duijvestijn A., Butcher E. C., Baisch H., Harder R., Thiele H. G. Evidence for an accessory role of LFA-1 in lymphocyte-high endothelium interaction during homing. J Immunol. 1988 Feb 1;140(3):693–699. [PubMed] [Google Scholar]
  12. Heider K. H., Hofmann M., Hors E., van den Berg F., Ponta H., Herrlich P., Pals S. T. A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. J Cell Biol. 1993 Jan;120(1):227–233. doi: 10.1083/jcb.120.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huet S., Groux H., Caillou B., Valentin H., Prieur A. M., Bernard A. CD44 contributes to T cell activation. J Immunol. 1989 Aug 1;143(3):798–801. [PubMed] [Google Scholar]
  14. Hughes E. N., Mengod G., August J. T. Murine cell surface glycoproteins. Characterization of a major component of 80,000 daltons as a polymorphic differentiation antigen of mesenchymal cells. J Biol Chem. 1981 Jul 10;256(13):7023–7027. [PubMed] [Google Scholar]
  15. Issekutz T. B., Stoltz J. M., vd Meide P. Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-gamma. J Immunol. 1988 May 1;140(9):2989–2993. [PubMed] [Google Scholar]
  16. Jalkanen S. T., Bargatze R. F., Herron L. R., Butcher E. C. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur J Immunol. 1986 Oct;16(10):1195–1202. doi: 10.1002/eji.1830161003. [DOI] [PubMed] [Google Scholar]
  17. Jalkanen S., Bargatze R. F., de los Toyos J., Butcher E. C. Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells. J Cell Biol. 1987 Aug;105(2):983–990. doi: 10.1083/jcb.105.2.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kaplan G., Cohn Z. A., Smith K. A. Rational immunotherapy with interleukin 2. Biotechnology (N Y) 1992 Feb;10(2):157–162. doi: 10.1038/nbt0292-157. [DOI] [PubMed] [Google Scholar]
  19. Koopman G., Heider K. H., Horst E., Adolf G. R., van den Berg F., Ponta H., Herrlich P., Pals S. T. Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44. J Exp Med. 1993 Apr 1;177(4):897–904. doi: 10.1084/jem.177.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lacy B. E., Underhill C. B. The hyaluronate receptor is associated with actin filaments. J Cell Biol. 1987 Sep;105(3):1395–1404. doi: 10.1083/jcb.105.3.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lesley J., He Q., Miyake K., Hamann A., Hyman R., Kincade P. W. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med. 1992 Jan 1;175(1):257–266. doi: 10.1084/jem.175.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marchal G., Seman M., Milon G., Truffa-Bachi P., Zilberfarb V. Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte. J Immunol. 1982 Sep;129(3):954–958. [PubMed] [Google Scholar]
  24. Martin S., Maruta K., Burkart V., Gillis S., Kolb H. IL-1 and IFN-gamma increase vascular permeability. Immunology. 1988 Jun;64(2):301–305. [PMC free article] [PubMed] [Google Scholar]
  25. Matsumura Y., Tarin D. Significance of CD44 gene products for cancer diagnosis and disease evaluation. Lancet. 1992 Oct 31;340(8827):1053–1058. doi: 10.1016/0140-6736(92)93077-z. [DOI] [PubMed] [Google Scholar]
  26. Miyake K., Medina K. L., Hayashi S., Ono S., Hamaoka T., Kincade P. W. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. doi: 10.1084/jem.171.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nakache M., Berg E. L., Streeter P. R., Butcher E. C. The mucosal vascular addressin is a tissue-specific endothelial cell adhesion molecule for circulating lymphocytes. Nature. 1989 Jan 12;337(6203):179–181. doi: 10.1038/337179a0. [DOI] [PubMed] [Google Scholar]
  28. Oppenheimer-Marks N., Davis L. S., Lipsky P. E. Human T lymphocyte adhesion to endothelial cells and transendothelial migration. Alteration of receptor use relates to the activation status of both the T cell and the endothelial cell. J Immunol. 1990 Jul 1;145(1):140–148. [PubMed] [Google Scholar]
  29. Phanuphak P., Moorhead J. W., Claman H. N. Tolerance and contact sensitivity to DNFB in mice. I. In vivo detection by ear swelling and correlation with in vitro cell stimulation. J Immunol. 1974 Jan;112(1):115–123. [PubMed] [Google Scholar]
  30. Rothman B. L., Blue M. L., Kelley K. A., Wunderlich D., Mierz D. V., Aune T. M. Human T cell activation by OKT3 is inhibited by a monoclonal antibody to CD44. J Immunol. 1991 Oct 15;147(8):2493–2499. [PubMed] [Google Scholar]
  31. Roupe G., Ridell B. The cellular infiltrate in contact hypersensitivity to picryl chloride in the mouse. Acta Derm Venereol. 1979;59(3):191–195. [PubMed] [Google Scholar]
  32. Sarmiento M., Dialynas D. P., Lancki D. W., Wall K. A., Lorber M. I., Loken M. R., Fitch F. W. Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis. Immunol Rev. 1982;68:135–169. doi: 10.1111/j.1600-065x.1982.tb01063.x. [DOI] [PubMed] [Google Scholar]
  33. Scheynius A., Camp R. L., Puré E. Reduced contact sensitivity reactions in mice treated with monoclonal antibodies to leukocyte function-associated molecule-1 and intercellular adhesion molecule-1. J Immunol. 1993 Jan 15;150(2):655–663. [PubMed] [Google Scholar]
  34. Shannon B. T., Love S. H., Myrvik Q. N. Participation of hyaluronic acid in the macrophage disappearance reaction. Immunol Commun. 1980;9(4):357–370. doi: 10.3109/08820138009052982. [DOI] [PubMed] [Google Scholar]
  35. Shimizu Y., Van Seventer G. A., Siraganian R., Wahl L., Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed] [Google Scholar]
  36. Springer T., Galfrè G., Secher D. S., Milstein C. Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens. Eur J Immunol. 1978 Aug;8(8):539–551. doi: 10.1002/eji.1830080802. [DOI] [PubMed] [Google Scholar]
  37. Stamenkovic I., Aruffo A., Amiot M., Seed B. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J. 1991 Feb;10(2):343–348. doi: 10.1002/j.1460-2075.1991.tb07955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sy M. S., Guo Y. J., Stamenkovic I. Distinct effects of two CD44 isoforms on tumor growth in vivo. J Exp Med. 1991 Oct 1;174(4):859–866. doi: 10.1084/jem.174.4.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Takei F. Inhibition of mixed lymphocyte response by a rat monoclonal antibody to a novel murine lymphocyte activation antigen (MALA-2). J Immunol. 1985 Mar;134(3):1403–1407. [PubMed] [Google Scholar]
  40. Telen M. J., Eisenbarth G. S., Haynes B. F. Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene. J Clin Invest. 1983 Jun;71(6):1878–1886. doi: 10.1172/JCI110943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
  42. Webb D. S., Shimizu Y., Van Seventer G. A., Shaw S., Gerrard T. L. LFA-3, CD44, and CD45: physiologic triggers of human monocyte TNF and IL-1 release. Science. 1990 Sep 14;249(4974):1295–1297. doi: 10.1126/science.1697984. [DOI] [PubMed] [Google Scholar]

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