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. 1993 Aug;143(2):587–597.

Development of functional diversity in mouse macrophages. Mutual exclusion of two phenotypic states.

D J Laszlo 1, P M Henson 1, L K Remigio 1, L Weinstein 1, C Sable 1, P W Noble 1, D W Riches 1
PMCID: PMC1887021  PMID: 8342604

Abstract

The objective of this study was to investigate the mechanisms that contribute to the generation of macrophage functional diversity. Exposure of mouse bone marrow-derived macrophages to beta-1,3-glucan, a particulate inflammatory stimulus, or polyinosinate-polycytidylate (poly[I:C]), a stimulus of macrophage cytocidal activation, induced distinct and stimulus-specific patterns of gene expression. These changes were characterized by an up-regulation of the expression of the acid hydrolase beta-glucuronidase and platelet-derived growth factor B following incubation with beta-1,3-glucan and a stimulation of the expression of the complement component Bf, beta-interferon, and the reactive nitrogen intermediates NO2/NO3 during incubation with poly[I:C]. The induction of Bf expression by poly[I:C] could not be explained on the basis of distinct subpopulations of cells since in situ hybridization with a mouse Bf cRNA probe revealed a uniform and substantial increase in Bf expression by the entire population of cells. Incubation of macrophages with beta-1,3-glucan before stimulation with poly[I:C] was found to strongly attenuate the expression of Bf and beta-interferon. Conversely, incubation with poly[I:C] prior to exposure to beta-1,3-glucan substantially blocked the stimulation of beta-glucuronidase and platelet-derived growth factor B expression, indicating that these two responses were expressed in a mutually antagonistic fashion. However, after removal of either stimulus and following a period in which the primary response was allowed to decay, the cells regained their capacity to subsequently respond to either the same stimulus or to a different stimulus. Collectively, these findings indicate, first, that the heterogeneity of gene expression seen in response to poly[I:C] represents an adaptive response of the entire macrophage population rather than the restricted responses of distinct subpopulations of cells. Second, macrophages respond to these stimuli in a sequential fashion. These findings thus have a significant bearing on our understanding of the regulation of macrophage heterogeneity in host defense.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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