ABSTRACT
Blood monocytes represent precursors for tissue-specifi c macrophages and dendritic cells. By expression of L-selectin, monocytes can be grouped into subsets with distinct functions in vivo (Geissmann et al. 2008). Th e fi rst subset expressing L-selectin in combination with M-CSF receptor (CD115), Ly6c, CCR2 has infl ammatory phenotype. L-selectin expressing cells are selectively recruited to infl amed tissues and lymph nodes and diff erentiate into infl ammatory dendritic cells. Th ese monocytes function as critical eff ector cells in primary and secondary immune responses. It has also been shown that L-selectin-positive subset could be expanded and polarized to inhibit T cell-mediated immunity. Th e second subset of monocytes is smaller and lacks expression of L-selectin, Ly6c, and CCR2. Th e L-selectin-negative subset is called resident or patrolling monocytes. Th ese monocytes require fi rm binding to endothelium mediated by the β2-integrins. Binding of monocytes to ECM is accomplished by β1-integrins represented by α1β1, α2β1, α4β1, α5β1, and α6 β1. Additionally, αMβ2-integrin is present in all monocytes. Th e constitutive expression is observed for α4β1, α5β1, and α6 β1, while activation of monocytes results in the expression of α1β1-as well as αvβ3-and α4β7-integrins. Adhesion of monocytes to ECM proteins changes the expression pattern of integrins, induces expression of pro-infl ammatory molecules through downstream activation of NF-κB pathway and also promotes cell migration and phagocytosis (Fig. 4). Macrophages express a vast number of receptors that mediate recognition of extracellular and intracellular pathogens followed by phagocytosis/endocytosis. Th e opsonic receptors include complement receptors (CR3, αMβ2/αXβ2) and Fc receptors (FcRs). Macrophages express also non-opsonic receptors mediating pathogen recognition, namely toll-like receptors (TLR) (Dale et al. 2008). By interacting with these receptors, integrins mediate innate and acquired immunity, participating in recognition of external danger signals and in activating FcRs by previously produced antibodies. Accumulation of this information in monocytes/ macrophages makes further rearrangements in primary and secondary T cell responses (Geissmann et al. 2008). For interaction between integrins and FcRs and TLR, see below. Several subpopulations of macrophages have been produced from the common mononuclear progenitor identifi ed upon expression of αMβ2/αXβ2 by direct stimulation with colony stimulating factors, including M-CSF, GM-CSF, and Flt3-ligand. Functional role of αMβ2/αXβ2 for potentiating eff ects from growth factors has been suggested (Shi and Simon 2006). A direct implication of αXβ2 in macrophage maturation and antigen presentation has been recently proved using αXβ2-diphtheria toxin receptor transgenic mice. Monocytic precursors of infl ammatory dendritic cells are defi ned as a population expressing αXβ2. However, the role of αXβ2 in diff erentiation and antigen presenting function of dendritic cells has been recently questioned.
