SummaryPlatelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is crucial to the process of leukocyte transmigration through intercellular junctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of monocytes by 70-90%. Pretreating either the monocytes or the endothelial junctions with antibody blocks transmigration. If the endothelium is first activated by cytokines, anti-PECAM antibody or soluble recombinant PECAM again block transmigration of both monocytes and neutrophils. Anti-PECAM does not block chemotaxis of either cell type. Light and electron microscopy reveal that leukocytes blocked in transmigration remain tightly bound to the apical surface of the endothelial cell, precisely over the intercellular junction. Thus, the process of leukocyte emigration can be dissected into three successive stages: rolling, mediated by the selectin dass of adhesion molecules; tight adhesion, mediated by the leukocyte integrins and their endothelial cell counter-receptors; and now transmigration, which, based on these studies, requires PECAM-1.

Summal'yA murine model of peritonitis was used to test the role of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) in acute inflammation. A monoclonal antibody (mAb) specific for murine PECAM-1 injected intravenously 4 h before the intraperitoneal injection of thioglycollate broth blocked leukocyte emigration into the peritoneal cavity for up to 48 h. This block was particularly evident for neutrophils. Control mAb, including one that bound to murine CD18 without blocking its function, failed to block emigration when used at the same or higher concentrations. The decreased emigration seen with the anti-PECAM-1 antibody was not due to neutropenia or neutrophil sequestration in the lung, spleen, or other organs; peripheral blood leukocyte counts were not diminished in these mice. In the mesenteric venules of the mice treated with anti-PECAM-1 mAb, leukocytes were frequently seen in association with the luminal surface of the vessel, but did not appear to emigrate. Thus, the requirement for PECAM-1 in the transendothelial migration of leukocytes previously seen in an in vitro model holds true in this in vivo model of acute inflammation.p latelet/endothelial cell adhesion molecule 1 (PECAM-1/ CD31) is a member of the Ig gene superfamily (1) concentrated at the intercellular junctions of cultured human endothelial cells (HEC) (2) and expressed on the surface of platelets (1) and most leukocytes. We have demonstrated that PECAM-1 is required for the migration of monocytes and neutrophils across resting and cytokine-activated HEC in a quantitative in vitro assay of transmigration (3).Recent characterization of the murine homolog of PECAM-1 has afforded us the opportunity to test the role of this molecule in an in vivo model of inflammation. Cloning of the routine homolog of PECAM-1 (4) revealed a predicted amino acid sequence with 79% homology to human CD31. L cells transfected with murine PECAM-1 cDNA aggregated in a PECAM-l-dependent manner, similar to human PECAM-1 transfectants. A mAb raised in hamsters that recognizes the murine form of CD31 (5) blocked this aggregation (4). Furthermore, immunohistochemical studies using this antibody demonstrated that murine PECAM-1 had a tissue distribution similar to that of human PECAM-1 (5).We used a murine model of acute peritonitis to test whether intravenously administered anti-murine PECAM-1 mAb would block acute inflammation. The results demonstrate that anti-PECAM-1 mAb inhibits emigration of neutrophils (PMN) to nearly background levels, establishing PECAM-1 as an important adhesion molecule in the inflammatory response. Materials and MethodsAnimals. Female mice of the CD2F1 strain weighing '~20 g were purchased from Charles River Laboratories (Boston, MA) and housed at The Rockefeller University Laboratory Animal Research Center. Female mice of the AKR/J strain were purchased from The Jackson Laboratory (Bar Harbor, ME) and housed at the Boston University School of Medicine Laboratory Animal Science Center. All animal procedures had been approved by the R...

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.

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