Abstract
Leukotrienes B4, C4, and D4, members of a recently discovered family of substances biosynthesized from arachidonic acid, were found to have potent microvascular actions in the hamster cheek pouch. When applied topically to the vascular network, leukotrienes C4 and D4 caused an intense constriction of arterioles, being similar to angiotensin in potency in this respect. The vasoconstriction induced by leukotrienes C4 and D4 was short-lived, and it was consistently followed by a marked and dose-dependent extravasation of macromolecules from postcapillary venules. Histamine did not constrict arterioles, but it elicited leakage of plasma, although on a molar basis it was no more than 1/1000th as potent as the leukotrienes. When used in the same concentration range as leukotrienes C4 and D4, leukotriene B4 did not evoke vasoconstriction or promote plasma leakage. On the other hand, leukotriene B4 caused a conspicuous and reversible adhesion of leukocytes to the endothelium in postcapillary venules. Our findings that leukotrienes induce microcirculatory alterations in vivo, closely resembling the early events in the acute inflammatory response, imply that leukotrienes, formed in several blood-borne and tissue-bound cells, may mediate important microcirculatory adjustments to noxious stimuli.
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- Arfors K. E., Bergqvist D., Intaglietta M., Westergren B. Measurements of blood flow velocity in the microcirculation. Ups J Med Sci. 1975;80(1):27–33. doi: 10.3109/03009737509178987. [DOI] [PubMed] [Google Scholar]
- Atherton A., Born G. V. Quantitative investigations of the adhesiveness of circulating polymorphonuclear leucocytes to blood vessel walls. J Physiol. 1972 Apr;222(2):447–474. doi: 10.1113/jphysiol.1972.sp009808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bach M. K., Brashler J. R., Hammarström S., Samuelsson B. Identification of a component of rat mononuclear cell SRS as leukotriene D. Biochem Biophys Res Commun. 1980 Apr 29;93(4):1121–1126. doi: 10.1016/0006-291x(80)90605-1. [DOI] [PubMed] [Google Scholar]
- Bach M. K., Brashler J. R., Hammarström S., Samuelsson B. Identification of leukotriene C-1 as a major component of slow-reacting substance from rat mononuclear cells. J Immunol. 1980 Jul;125(1):115–117. [PubMed] [Google Scholar]
- Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dahlén S. E., Hedqvist P., Hammarström S., Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature. 1980 Dec 4;288(5790):484–486. doi: 10.1038/288484a0. [DOI] [PubMed] [Google Scholar]
- Del Maestro R., Thaw H. H., Björk J., Planker M., Arfors K. E. Free radicals as mediators of tissue injury. Acta Physiol Scand Suppl. 1980;492:43–57. [PubMed] [Google Scholar]
- Drazen J. M., Austen K. F., Lewis R. A., Clark D. A., Goto G., Marfat A., Corey E. J. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4354–4358. doi: 10.1073/pnas.77.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duling B. R. The preparation and use of the hamster cheek pouch for studies of the microcirculation. Microvasc Res. 1973 May;5(3):423–429. doi: 10.1016/0026-2862(73)90059-9. [DOI] [PubMed] [Google Scholar]
- Ford-Hutchinson A. W., Bray M. A., Doig M. V., Shipley M. E., Smith M. J. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature. 1980 Jul 17;286(5770):264–265. doi: 10.1038/286264a0. [DOI] [PubMed] [Google Scholar]
- Fulton G. P., Jackson R. G., Lutz B. R. Cinephotomicroscopy of Normal Blood Circulation in the Cheek Pouch of the Hamster. Science. 1947 Apr 4;105(2727):361–362. doi: 10.1126/science.105.2727.361. [DOI] [PubMed] [Google Scholar]
- Hedqvist P., Dahlén S. E., Gustafsson L., Hammarström S., Samuelsson B. Biological profile of leukotrienes C4 and D4. Acta Physiol Scand. 1980 Nov;110(3):331–333. doi: 10.1111/j.1748-1716.1980.tb06676.x. [DOI] [PubMed] [Google Scholar]
- Holme G., Brunet G., Piechuta H., Masson P., Girard Y., Rokach J. The activity of synthetic leukotriene C-1 on guinea pig trachea and ileum. Prostaglandins. 1980 Oct;20(4):717–728. doi: 10.1016/0090-6980(80)90110-0. [DOI] [PubMed] [Google Scholar]
- Hoover R. L., Briggs R. T., Karnovsky M. J. The adhesive interaction between polymorphonuclear leukocytes and endothelial cells in vitro. Cell. 1978 Jun;14(2):423–428. doi: 10.1016/0092-8674(78)90127-7. [DOI] [PubMed] [Google Scholar]
- Houglum J., Pai J. K., Atrache V., Sok D. E., Sih C. J. Identification of the slow reacting substances from cat paws. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5688–5692. doi: 10.1073/pnas.77.10.5688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis R. A., Drazen J. M., Austen K. F., Clark D. A., Corey E. J. Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activity. Biochem Biophys Res Commun. 1980 Sep 16;96(1):271–277. doi: 10.1016/0006-291x(80)91210-3. [DOI] [PubMed] [Google Scholar]
- MAJNO G., PALADE G. E., SCHOEFL G. I. Studies on inflammation. II. The site of action of histamine and serotonin along the vascular tree: a topographic study. J Biophys Biochem Cytol. 1961 Dec;11:607–626. doi: 10.1083/jcb.11.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MILES A. A., MILES E. M. Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs. J Physiol. 1952 Oct;118(2):228–257. doi: 10.1113/jphysiol.1952.sp004789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majno G., Shea S. M., Leventhal M. Endothelial contraction induced by histamine-type mediators: an electron microscopic study. J Cell Biol. 1969 Sep;42(3):647–672. doi: 10.1083/jcb.42.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malmsten C. L., Palmblad J., Udén A. M., Rådmark O., Engstedt L., Samuelsson B. Leukotriene B4: a highly potent and stereospecific factor stimulating migration of polymorphonuclear leukocytes. Acta Physiol Scand. 1980 Dec;110(4):449–451. doi: 10.1111/j.1748-1716.1980.tb06696.x. [DOI] [PubMed] [Google Scholar]
- Morris H. R., Taylor G. W., Piper P. J., Samhoun M. N., Tippins J. R. Slow reacting substances (SRSs): the structure identification of SRSs from rat basophil leukaemia (RBL-1) cells. Prostaglandins. 1980 Feb;19(2):185–201. doi: 10.1016/0090-6980(80)90019-2. [DOI] [PubMed] [Google Scholar]
- Morris H. R., Taylor G. W., Piper P. J., Tippins J. R. Structure of slow-reacting substance of anaphylaxis from guinea-pig lung. Nature. 1980 May 8;285(5760):104–106. doi: 10.1038/285104a0. [DOI] [PubMed] [Google Scholar]
- Murphy R. C., Hammarström S., Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4275–4279. doi: 10.1073/pnas.76.9.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orange R. P., Austen K. F. Slow reacting substance of anaphylaxis. Adv Immunol. 1969;10:105–144. doi: 10.1016/s0065-2776(08)60416-2. [DOI] [PubMed] [Google Scholar]
- Orning L., Hammarström S. Inhibition of leukotriene C and leukotriene D biosynthesis. J Biol Chem. 1980 Sep 10;255(17):8023–8026. [PubMed] [Google Scholar]
- Orning L., Hammarström S., Samuelsson B. Leukotriene D: a slow reacting substance from rat basophilic leukemia cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2014–2017. doi: 10.1073/pnas.77.4.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palmer R. M., Stepney R. J., Higgs G. A., Eakins K. E. Chemokinetic activity of arachidonic and lipoxygenase products on leuocyctes of different species. Prostaglandins. 1980 Aug;20(2):411–418. doi: 10.1016/s0090-6980(80)80058-x. [DOI] [PubMed] [Google Scholar]
- Rouzer C. A., Scott W. A., Cohn Z. A., Blackburn P., Manning J. M. Mouse peritoneal macrophages release leukotriene C in response to a phagocytic stimulus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4928–4932. doi: 10.1073/pnas.77.8.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samuelsson B., Borgeat P., Hammarström S., Murphy R. C. Introduction of a nomenclature: leukotrienes. Prostaglandins. 1979 Jun;17(6):785–787. doi: 10.1016/0090-6980(79)90052-2. [DOI] [PubMed] [Google Scholar]
- Samuelsson B., Borgeat P., Hammarström S., Murphy R. C. Leukotrienes: a new group of biologically active compounds. Adv Prostaglandin Thromboxane Res. 1980;6:1–18. [PubMed] [Google Scholar]
- Samuelsson B., Hammarström S., Murphy R. C., Borgeat P. Leukotrienes and slow reacting substance of anaphylaxis (SRS-A). Allergy. 1980 Jul;35(5):375–381. doi: 10.1111/j.1398-9995.1980.tb01782.x. [DOI] [PubMed] [Google Scholar]
- Samuelsson B., Hammarström S. Nomenclature for leukotrienes. Prostaglandins. 1980 May;19(5):645–648. doi: 10.1016/0090-6980(80)90099-4. [DOI] [PubMed] [Google Scholar]
- Smith M. J., Ford-Hutchinson A. W., Bray M. A. Leukotriene B: a potential mediator of inflammation. J Pharm Pharmacol. 1980 Jul;32(7):517–518. doi: 10.1111/j.2042-7158.1980.tb12985.x. [DOI] [PubMed] [Google Scholar]
- Sok D. E., Pai J. K., Atrache V., Sih C. J. Characterization of slow reacting substances (SRSs) of rat basophilic leukemia (RBL-1) cells: effect of cysteine on SRS profile. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6481–6485. doi: 10.1073/pnas.77.11.6481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Svensjö E., Arfors K. E., Arturson G., Rutili G. The hamster cheek pouch preparation as a model for studies of macromolecular permeability of the microvasculature. Ups J Med Sci. 1978;83(1):71–79. doi: 10.3109/03009737809179115. [DOI] [PubMed] [Google Scholar]