Role of adhesion glycoproteins CD 18 and intercellular adhesion molecule‐1 in complement‐mediated reactions of rabbit skin

Abstract

The role of the adhesion glycoproteins CD 18 and intercellular adhesion molecule‐1 (ICAM‐1) in inflammatory responses produced during a reversed passive Arthus (RPA) reaction and induced by zymosan and zymosan‐activated plasma (ZAP) were studied in rabbit skin. Oedema formation and haemorrhage were quantified by measuring accumulation of 125I‐albumin and 111In‐labelled red blood cells (111In‐RBC) respectively. Monoclonal antibody (mAb) R15.7 (anti‐CD18), administered intravenously, abolished accumulation of 125I‐albumin and 111In‐RBC in dermal RPA reactions and in response to locally injected zymosan and ZAP. When administered intravenously, the mAb RR1/1 (anti‐ICAM‐1) suppressed 125I‐albumin and 111In‐RBC accumulation in dermal RPA reactions and at sites treated with zymosan and ZAP. Oedema formation in response to platelet‐activating factor (PAF) and bradykinin (BK) either in the presence or absence of prostaglandin E2 (PGE2) were not affected by mAb R15.7 or by mAb RR1/1.1.1. We conclude that oedema formation and haemorrhage associated with RPA reactions and in responses to zymosan and ZAP are completely CD 18‐dependent, and are mediated, at least in part, via ICAM‐1. Responses to the neutrophil‐independent oedema forming mediators, PAF and BK are not dependent upon CD 18 or ICAM‐1.

Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea‐pig skin: contribution of neutrophils and endogenous mediators

“…injection of inflammatory mediators such as FMLP or C5a in rabbit skin induces oedema formation which is abrogated when circulating neutrophils are depleted (Wedmore & Williams, 1981b;Hellewell et al, 1989) or when neutrophil accumulation is inhibited by pretreatment with mAbs that recognize the CD1 1/CD1 8 integrins on the surface of the neutrophil (Afors et al, 1987;Norman et al, 1994). Similarly, in rat and rabbit skin, oedema formation and haemorrhage in a cutaneous RPA reaction are dependent on neutrophils (Mulligan et al, 1992b;Norman et al, 1994). Our results obtained in investigating the neutrophil-------------dependency and the mechanisms involved in a RPA reaction in guinea-pig skin can be summarized as follows: (1) Most oedema formation in the RPA reaction occurred over the first 60 min whereas "'In-neutrophil accumulation was still rising from 60 to 240 min.…”

“…We could not measure "'Inneutrophils in experiments with 6.5E whole mAb since it has been previously shown to enhance the clearance of radiolabelled leukocytes from the circulation . Similarly, anti-CD18 treatment in rabbits and rats has been shown to inhibit not only neutrophil accumulation and haemorrhage, but also oedema formation (Mulligan et al, 1992b;Norman et at., 1994). Thus, in guinea-pig skin, oedema formation in a RPA reaction is partially neutrophildependent, at least measured over 4 h. It is possible that oedema formation measured at later periods (7 to 48 h) may also be dependent on neutrophils as suggested by Humphrey (1955b).…”

“…In rabbit skin, depletion of circulating neutrophils with nitrogen mustard or anti-neutrophil serum effectively inhibits the extravasation of albumin and the consequent oedema formation (Stetson, 1951;Humphrey, 1955a). Similarly, the blockade of CD1I/CD18 integrins on the neutrophil surface using RI 5.7, a monoclonal antibody (mAb) which abrogates neutrophil accumulation in rabbit skin (Rampart et al, 1991), inhibits both the extravasation of albumin and red blood cells in the rabbit RPA reaction (Norman et al, 1994). In rat skin, another anti-CDII/CD18 mAb also suppresses oedema formation and haemorrhage in a RPA reaction (Mulligan et al, 1992b).…”

“…We have previously analyzed the mediators involved in RPA reactions in rabbit skin (Hellewell & Williams, 1986;Hellewell, 1990;Rossi et al, 1992) and the reliance of neutrophil-dependent oedema on CD18 (Norman et al, 1994). In this paper, we have also investigated the possible role of endogenous mediators of inflammation (prostaglandins, nitric oxide, histamine, PAF and leukotrienes) in inducing oedema formation and neutrophil accumulation in immune complex vasculitis in guinea-pig skin.…”

Effect of soluble P55 tumour‐necrosis factor binding fusion protein on the local Shwartzman and Arthus reactions

“…The RPA reaction and the LSR have, however, been demonstrated to be complement-and neutrophil-dependent (Stetson & Good, 1951; Humphrey, 1955;Cochrane & Janoff, 1974;Yeh et al, 1991;Rossi et al, 1992). Furthermore, the Arthus reaction Noonan et al, 1993;Norman et al, 1994;Teixeira et al, 1994) and the LSR (Argenbright & Barton 1991;1992) are inhibited by i.v. administration of mAbs directed against the leucocyte adhesion molecule CD18 and the predominantly endothelial cell adhesion molecule, intercellular adhesion molecule-i (ICAM-1).…”