Selective suppression of leukocyte recruitment in allergic inflammation

Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

The eosinophils in parasitic infections

Local and peripheal eosinophilia is a common feature of many helminth infections that present large, non-phagocytable surfaces to the inmune system. The effect of the eosinophils on these organisms has been studied in the last 18 years using schistosoma mansoni, trichinella spiralis, and other helminths as models. The early infection causes a nonspecific inflammation rich in macrophages, lymphocytes and neutrophils that sets the stage for a subsequent inmune response. The predominant effector elements of the inmune response are anaphylactic antibodies, mast cells, and eosinophils. Mast cell products attract eosinophils and concentrate antibodies and complement-covered parasites by their Fc and/or C3c receptors and release oxygen radicals and/or preformed proteins on the helmith surface. The radicals alter molecules of the parasite and the proteins disrupt its tegument or cuticle. Occasionally, they may harm host cells. Eosinophils also phagocytize and harm extracellular trypanosoma cruzi and may play a role in the damage to the host heart tissue. The eosinophil response is regulated by eosinophilopoietic factors (interleukines [IL] 3 and 5, and granulocyte macrophage colony-stimulating factor) eosinophilotactic factors (C5a from complement, eosinophil chemotactic factor of anaphylaxis [ECF-A], histamine, platelet stimulating factor, and other ECFs from mast cells and basophils, and ECF from parasites), and eosinophiloactivating factors (IL-5 from Th2 lymphocytes, tumor necrosis factor from macrophages, antibodies, and complement components). Other phagocytic cells (macrophages and neutrophils) also exhibit important anti-helminthic activities