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. 1992 Aug;76(4):655–661.

The contribution of LFA-1 (CD11a/CD18) and MAC-1 (CD11b/CD18) to the in vivo migration of polymorphonuclear leucocytes to inflammatory reactions in the rat.

A C Issekutz 1, T B Issekutz 1
PMCID: PMC1421555  PMID: 1398754

Abstract

Recently the critical requirement for the CD18 family of adhesion molecules on leucocytes for their adhesion and migration to inflammatory reactions has been recognized in humans and several animal models. The in vivo studies have mostly utilized antibodies to CD18, the common beta-subunit of CD11a,b,c/CD18 molecules and thus have blocked the function of all three family members, making evaluation of the role of individual subunits impossible. Furthermore, none of the reagents used were suitable for studies in rats. Here we report the effects on polymorphonuclear leucocyte (PMNL) adhesion and in vivo migration of a new monoclonal antibody (mAb) TA3, which recognizes and blocks rat CD11a/CD18 (LFA-1). These studies also evaluated mAb MRC OX42, which reacts with rat CD11b/CD18 (CR3, MAC-1). Neither antibody alone inhibited rat PMNL adhesion to interleukin-1 (IL-1)-activated rat endothelium, but the combination inhibited adhesion by 44%. OX42 treatment of rat PMNL inhibited phorbol myristate acetate (PMA) activated adhesion by 88%, while TA3 only inhibited this adhesion in combination with OX42, resulting in 99% inhibition of PMA-induced PMNL adhesion. Treatment of rats with TA3 alone partially inhibited 51Cr-labelled rat blood PMNL migration into zymosan-activated serum (C5adesArg; ZAS), but not IL-1, or endotoxin [lipopolysaccharide (LPS)] induced dermal inflammatory reactions. MAb OX42 had no such effect in vivo. However, treatment with both antibodies virtually eliminated any PMNL accumulation in all three types of inflammatory reactions. Ex vivo treatment of the 51Cr-labelled PMNL, prior to i.v. infusion showed that mAb TA3 again preferentially inhibited PMNL migration to ZAS. These results suggest that in the rat, CD11a/CD18 plays a major role in PMNL migration to C5a and that either CD11a or CD11b/CD18 can function to maintain normal PMNL migration to IL-1 or LPS dermal inflammatory reactions. More than one member of this adhesion family or their ligands may need to be targeted for effective modulation of PMNL infiltration, at least in this species.

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Selected References

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