INFLAMMATION AS A FUNDAMENTAL PATHOLOGICAL PROCESS: LECTURE 2 (CELLULAR COMPONENT)

The second part of the lecture describes cellular events occurring in the focus of inflammation. The first cells migrating to the focus of inflammation are neutrophils, the second are accumulate monocytes (macrophages), and the final cells of inflammation are fibroblasts. This sequence is determined by the spectrum of chemoattractants which are presented in the focus of inflammation.

Neutrophil migration is initiated by tissue macrophages, which are activated upon tissue damage and begin to secrete cytokines, primarily IL-8 and IL-1. These cytokines ensure neutrophil adhesion to the vascular wall and their further chemotaxis along the gradient of these cytokines and other chemoattractants. There are several populations of neutrophils. Inflammation mainly involves high density neutrophils (mature cells) and low density neutrophils (immature cells, e.g. band forms). From a functional point of view, neutrophils are divided into pro-inflammatory (N1) and immunosuppressive (N2), the balance between these cells is very important for an adequate course of inflammation. Neutrophils begin the process of destroying the pathogen and tissue damage products. In addition to the long-known phagocytosis, this process is carried out with the help of neutrophil extracellular traps (NET), which consist of DNA, histones and lysosomal enzymes. Neutrophils in the focus of inflammation synthesize cytokines (IL-1, IL-6, TNFα, G-CSF and others), which stimulate the migration of monocytes and their differentiation into macrophages. Activated macrophages are divided into two groups: classic pro-inflammatory M1 and alternative anti-inflammatory M2. M1 are involved in the elimination of pathogen. They have powerful cytotoxic and antimicrobial activities. M2 macrophages produce anti-inflammatory cytokines (IL-10, TGFβ, etc.), growth factors, they stimulate angiogenesis, fibroblast proliferation processes and the formation of an extracellular matrix by fibroblasts. Fibroblasts, attracted by macrophage cytokines, complete the inflammatory process. They synthesize the basic substance of the connective tissue and provide the process of its organization. Dysregulation of cellular responses can underlie chronic inflammation.

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