Abstract
CR3 and CR4, the leukocyte specific β2-integrins, involved in cellular adherence, migration and phagocytosis, are often assumed to have similar functions. Previously however, we proved that under physiological conditions CR4 is dominant in the adhesion to fibrinogen of human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Here, using inflammatory conditions, we provide further evidence that the expression and function of CR3 and CR4 are not identical in these cell types. We found that LPS treatment changes their expression differently on MDMs and MDDCs, suggesting a cell type specific regulation. Using mAb24, specific for the high affinity conformation of CD18, we proved that the activation and recycling of β2-integrins is significantly enhanced upon LPS treatment. Adherence to fibrinogen was assessed by two fundamentally different approaches: a classical adhesion assay and a computer-controlled micropipette, capable of measuring adhesion strength. While both receptors participated in adhesion, we demonstrated that CR4 exerts a dominant role in the strong attachment of MDDCs. Studying the formation of podosomes we found that MDMs retain podosome formation after LPS activation, whereas MDDCs lose this ability, resulting in a significantly reduced adhesion force and an altered cellular distribution of CR3 and CR4. Our results suggest that inflammatory conditions reshape differentially the expression and role of CR3 and CR4 in macrophages and dendritic cells.
Highlights
The complement receptors CR3 (CD11b/CD18, known as Mac-1; αMβ2) and CR4 (CD11c/CD18, known as p150,95; αXβ2) belong to the family of β2-integrins and play an important role in phagocytosis, cellular adherence and migration [1]
Comparing the amount of CR3 and CR4 on the cell surface we found that LPS treatment alters their expression differently on monocyte-derived macrophages (MDMs) and MDDCs (Fig 1)
LPS treatment enhances β2-integrin cycling in both MDMs and MDDCs
Summary
The complement receptors CR3 (CD11b/CD18, known as Mac-1; αMβ2) and CR4 (CD11c/CD18, known as p150,95; αXβ2) belong to the family of β2-integrins and play an important role in phagocytosis, cellular adherence and migration [1] Their ligands include iC3b, the activation product of complement component C3, present on opsonized targets, as well as the adhesion ligands fibrinogen and ICAM-1 [2,3,4]. Based on findings showing that CR3 and CR4 have overlapping ligand binding specificity and share 87% sequence homology in their extracellular domains [7], these two receptors are generally assumed to exert similar functions. We demonstrated that CR3 is in control of the phagocytosis of iC3b opsonized bacteria while CR4 dominates cell adhesion to fibrinogen [11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
