Suppression of Late Phase Enhanced Vascular Permeability in Rats by Selective Depletion of Neutrophils With a Monoclonal Antibody

Abstract

We investigated the role of neutrophils in increased vascular permeability by a selective reduction of neutrophils using a monoclonal antibody, RP-3. An intraperitoneal injection of RP-3 not only selectively depleted peripheral blood neutrophils, but prevented the neutrophil infiltration to the tissues. Proteose peptone, zymosan, and BCG induced three different types of inflammatory edema, showing the early phase only, early plus late phase, and the late phase only, respectively. Only the late phase response of zymosan and BCG was inhibited by a depletion of neutrophils by RP-3, though the early phase response induced by proteose peptone and zymosan was not affected. Reconstitution of neutrophil-depleted rats by in situ injection of these cells restored the inflammatory edema induced by BCG, depending upon the number of neutrophils injected.

Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

“…RP3 selectively reacts and depletes rat neutrophils but not other nucleated blood cells on in vivo administration. 24 - 25 Depletion of neutrophils with RP3 inhibited the late phase response of inflammatory edema in rats. 25 To assess the influence of depletion of circulating neutrophils on neutrophil infiltration, brain edema formation, and size of infarct area after ischemia, rats were given 3 mL of the ascitic fluid containing RP3 or vehicle (saline, 3 mL per animal) intraperitoneally, 24 hours before and immediately after ischemic insult.…”

“…24 - 25 Depletion of neutrophils with RP3 inhibited the late phase response of inflammatory edema in rats. 25 To assess the influence of depletion of circulating neutrophils on neutrophil infiltration, brain edema formation, and size of infarct area after ischemia, rats were given 3 mL of the ascitic fluid containing RP3 or vehicle (saline, 3 mL per animal) intraperitoneally, 24 hours before and immediately after ischemic insult. The dose of RP3 chosen in this study is a sufficient dose to induce almost complete depletion of neutrophils from 6 hours to over 24 hours after administration and does not affect other blood cells.…”

“…24 - 25 The ascitic fluid containing a high titer of RP3 was used as an antibody source in the experiment. RP3 selectively reacts and depletes rat neutrophils but not other nucleated blood cells on in vivo administration.…”

“…- 25 Brain water content and MPO activity after 24 hours of reperfusion were measured as described above. To measure the size of infarct area, rats were perfused with physiological saline containing 0.2% heparin after 24 hours of reperfusion.…”

IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy

“…The immediate VP is proved to be dependent on histamine, serotonin, bradykinin, prostaglandins, and plateletactivating factor [1][2][3], whereas little is known about the mediator(s) for the delayed VP. Several lines of evidence suggest that the delayed VP is associated with neutrophil infiltration [3][4][5][6]. Factors that mediate the delayed VP, however, remain unknown.…”