CD100 and plexins B2 and B1 mediate monocyte-endothelial cell adhesion and might take part in atherogenesis

Abstract

Leukocyte migration is essential for the function of the immune system. Their recruitment from the vessels to the tissues involves sequential molecular interactions between leukocytes and endothelial cells (ECs). Many adhesion molecules involved in this process have already been described. However, additional molecules may be important in this interaction, and here we explore the potential role for CD100 and plexins in monocyte-EC binding. CD100 was shown to be involved in platelet-endothelial cell interaction, an important step in atherogenesis and thrombus formation. In a recent work we have described CD100 expression in monocytes and in macrophages and foam cells of human atherosclerotic plaques. In the present work, we have identified plexin B2 as a putative CD100 receptor in these cells. We have detected CD100 expression in the endothelium as well as in in vitro cultured endothelial cells. Blocking of CD100, plexin B1 and/or B2 in adhesion experiments have shown that both CD100 and plexins act as adhesion molecules involved in monocyte-endothelial cell binding. This effect may be mediated by CD100 expressed in both cell types, probably coupled to the receptors endothelial plexin B1 and monocytic plexin B2. These results can bring new insights about a possible biological activity of CD100 in monocyte adhesion and atherosclerosis, as well as a future candidate for targeting therapeutics.

γ-Aminobutyric Acid Is Synthesized and Released by the Endothelium

“…26 HUVEC were grown to 80% confluency in specific petridishes and treated with drugs as indicated in the results under flow conditions by the introduction of mechanical-sheer stress (125 dynes/cm 2 ) as described earlier. 27 Thereafter cells were washed twice with fresh media and incubated with monocytes (THP1) pretreated with 2.5 μmol/L Calcein AM for 1 hour.…”

Immunomodulatory Functions of Neuronal Guidance Proteins

“…This finding was corroborated by a study by Luque et al that demonstrated that monocytes are retained on endothelial cells via the Sema4D-Plexin B1 axis [85]. In human samples of carotid artery plaques, the expression of Sema4D was enhanced, yet incubation with Sema4D reduced the formation of foam cells [85]. These studies point to a potential role of semaphorin-plexin interactions during the development of atherosclerotic lesions.…”

“…Sema3E is upregulated in the macrophages of advanced plaques and acts as a negative regulator of macrophage migration, promoting macrophage retention and chronic inflammation [84]. This finding was corroborated by a study by Luque et al that demonstrated that monocytes are retained on endothelial cells via the Sema4D-Plexin B1 axis [85]. In human samples of carotid artery plaques, the expression of Sema4D was enhanced, yet incubation with Sema4D reduced the formation of foam cells [85].…”

Caracterização funcional de CD100/Sema4D na infecção de macrófagos por <i>Leishmania</i> (<i>Leishmania</i>) <i>amazonensis</i>.

“…Essa proteína é encontrada como um dímero ligado à membrana no tamanho de 150 kDa (por subunidade) ou na forma solúvel no tamanho de 120 kDa (sCD100), obtida por clivagem (BASILE et al, 2007;ELHABAZI et al, 2003;ZHU et al, 2007). Essa clivagem é feita em plaquetas por uma metaloprotease ADAM17 (ZHU, 2007 (MOREAUFAUVARQUE et al, 2003), em crescimento e angiogênese tumorais (BASILE et al, 2006;CH'NG;KUMANOGOH, 2010;GABROVSKA et al, 2011;KATO et al, 2011;SIERRA et al, 2008;SOONG et al, 2011;YANG et al, 2011), em osteogênese (NEGISHI-KOGA et al, 2011) e em aterosclerose (LUQUE et al, 2013;LUQUE et al, 2015), e ainda foi mostrado que CD100 também é expressa em plaquetas, participando ora da formação de trombos, ora da recuperação da monocamada endotelial (ZHU et al, 2007). …”

“…Interessantemente, vimos que apenas parte dos macrófagos de baço expressam CD100, sugerindo que essa molécula possa estar relacionada com subtipos específicos de macrófagos (LUQUE et al, 2013). Em um segundo trabalho, mostramos que CD100 e as plexinas, especialmente plexina B2, contribuem para a ligação de monócitos humanos a células endoteliais in vitro, e que essas duas células expressam CD100 na membrana, apontando para a proteína como um dos participantes na interação célula endotelial-monócito, um passo importante na aterogênese e formação de trombos (LUQUE et al, 2015).…”