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American Journal of Pathology, Vol 145, 461-469, Copyright © 1994 by American Society for Investigative Pathology

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Monoclonal antibody blockade of L-selectin inhibits mononuclear leukocyte recruitment to inflammatory sites in vivo

P Pizcueta and FW Luscinskas
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.

L-selectin interacting with inducible endothelial counterreceptors mediates in part the initial adhesive interactions, termed rolling, between circulating blood leukocytes and vascular endothelium. While blockade of L-selectin function in in vivo models of inflammation reduces both neutrophil and lymphocyte influx at early times, little is known concerning the role of L-selectin in leukocyte recruitment at later times (> 24 hours). Using an in vivo murine model of experimentally induced inflammation of the peritoneum, the role of L- selectin in recruitment of mononuclear leukocytes to chronic sites of inflammation (48 hours) was investigated. Saturating levels of function blocking anti-L-selectin monoclonal antibody (MEL-14) or control rat IgG were maintained for 48 hours using surgically implanted mini- osmotic pumps; this treatment did not alter the circulating leukocyte cell count or differential. In animals receiving MEL-14 monoclonal antibody (MAb), macrophage and lymphocyte accumulation in response to thioglycollate was reduced by 60% (P < or = 0.0002) and > 90% (P < 0.001), respectively, at 48 hours as compared with animals implanted with pumps containing saline. Similarly, MEL-14 MAb dramatically inhibited granulocyte influx by 80% (P < 0.03) at 6 hours; recruitment at 24 and 48 hours was reduced by 50%. In contrast, the effects of purified rat IgG was not significantly different from saline. Our results suggest L-selectin, interacting with its inducible endothelial counterreceptor(s), plays an important role in circulating mononuclear leukocyte extravasation at sites of inflammation.

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