Role of CD18 in the accumulation of eosinophils and neutrophils and local oedema formation in inflammatory reactions in guinea‐pig skin

Abstract

Intradermal injection of the complement fragment C5a des Arg induces local oedema formation that, in rabbits and man, is dependent on circulating neutrophils. Monoclonal antibodies to the leukocyte adhesion molecule CD11/CD18 block neutrophil accumulation and prevent neutrophil‐dependent oedema formation. The role of CD11/CD18 in mediating eosinophil accumulation in vivo is less established. In this study we have used an anti‐human CD18 monoclonal antibody, 6.5E, to investigate the neutrophil‐dependency of oedema formation induced by C5a des Arg in guinea‐pig skin. We also studied the role of CD18 in mediating eosinophil accumulation in the same model. Stimulated adhesion of 111In‐labelled guinea‐pig neutrophils and eosinophils to serum‐coated plastic was inhibited in a dose‐dependent manner by 6.5E suggesting that the monoclonal antibody recognizes and blocks the guinea‐pig CD18 adhesion molecule. The accumulation of 111In‐labelled neutrophils induced by zymosan‐activated plasma (ZAP, as a source of C5a des Arg) in skin sites was reduced by up to 89% in animals treated intravenously with F(ab')2 fragments of 6.5E. ZAP‐induced accumulation of 111In‐labelled eosinophils was also greatly reduced (by up to 78%) by treatment with 6.5E. Despite the inhibition of ZAP‐induced neutrophil accumulation by 6.5E, local oedema formation in the same skin sites was unaffected, except at the top dose of ZAP, by treatment with the anti‐CD18 monoclonal antibody, suggesting that the oedema response was largely neutrophil‐independent. Indeed, ZAP‐induced oedema formation was reduced by up to 81% by the H1 receptor antagonist, mepyramine. Accumulation of 111In‐labelled eosinophils in a passive cutaneous anaphylactic (PCA) reaction was also blocked by treatment with 6.5E, while oedema formation in the same skin sites was unaffected. Intradermal injection of cationic protein‐containing extracts of Schistosoma mansoni larvae also induced the accumulation of 111In‐labelled neutrophils and eosinophils which was abrogated by intravenous 6.5E. In contrast, extract‐induced local oedema formation was similar in control and 6.5E‐treated guinea‐pigs. In summary, the local accumulation of radiolabelled neutrophils at sites of inflammation in guinea‐pig skin was dependent on the adhesion molecule CD18 while, in contrast, there was no evidence for neutrophil‐dependent oedema formation in this species. Accumulation of radiolabelled eosinophils was also dependent on CD18.

Distinct Roles for PECAM-1, ICAM-1, and VCAM-1 in Recruitment of Neutrophils and Eosinophils to the Cornea in Ocular Onchocerciasis (River Blindness)

“…The differences between those findings and results of the current study, where neither injection of anti-ICAM-1 nor ICAM-1 deficiency had any significant effect on neutrophil recruitment to the cornea, have yet to be determined. In contrast to neutrophils, the role of ICAM-1 expression in eosinophil extravasation is consistent with expression of LFA-1 ligand on eosinophils (31,32) and with reports in which ICAM-1 blockade inhibits the migration of eosinophils to the skin and the airways (33,34).…”

Mannheimia haemolyticaand Its Leukotoxin Cause Neutrophil Extracellular Trap Formation by Bovine Neutrophils

“…Previous reports have demonstrated that neutrophils from several vertebrate species, human eosinophils and mast cells, and chicken heterophils all form extracellular traps (12,13,19,34,38,43,48,49,68,73). All these cells express CD18, which is involved in transendothelial migration of leukocytes from the bloodstream into tissue at sites of infection (45,47,54,60,61,75). Because CD18 is expressed by cell types capable of forming extracellular traps, Previous research demonstrated that only 10 to 33% of human neutrophils formed NETs in response to a single exposure to a stimulus in vitro (13,31).…”

Differential role of neutrophils and monocytes during subcutaneous plasma extravasation

“…21,22 However, our current study using the PMN-depleted animal clearly demonstrated that the ZAP-induced plasma protein extravasation in guinea-pig skin is composed of two different mechanisms, one PMN-dependent and the other PMN-independent. This result is consistent with the previous report using the rabbit skin.…”

“…21,22 So, we examined whether the ZAP-induced PMN-independent plasma extravasation could be suppressed with an antihistaminic agent, triprolidine. To evaluate the effect exclusively on the PMN-independent response, we measured the plasma extravasation for initial 30 min in the PMN-depleted guinea-pigs pretreated with cyclophosphamide.…”