Shear‐Induced Cleavage of CD18 Integrins on Human Granulocytes, Monocytes and Lymphocytes

Shear stress generated by blood flow serves as a negative regulator of cell activity by activating and cleaving CD18 on circulating leukocytes. Leukocytes composed of granulocytes, monocytes and lymphocytes participate in different aspects of the immune response as reflected, in part, by their differential expression of CD11a/CD18 and CD11b/CD18 that serve as putative flow sensors. We hypothesized that shear‐induced CD18 cleavage on leukocytes is cell type‐specific depending on their respective surface expression of CD11a and CD11b integrins. To test this, human leukocytes were sheared (2.5 – 10 dyn/cm 2 ) with a cone‐plate viscometer for up to 10 min and assessed for their surface expression of CD11a, CD11b, and CD18. Shear stress reduced surface levels of CD11b but not CD11a integrins on granulocytes. Surface expression of CD11a integrins, however, was reduced by shear for lymphocytes that do not express detectable amounts of CD11b/CD18. Monocytes did not exhibit significant reductions of CD11a or CD11b integrins. These results point to shear‐induced cleavage of CD11b over CD11a integrins depending on their respective surface levels. Our results suggest that leukocyte mechanotransduction depends, at least in part, on surface expression of possible mechanosensors and thus provide insight in the control of leukocyte activity by the circulation. Supported by the AHA and NSF‐EPSCoR of Kentucky.