Leukocytes chemotaxis

Lacalle RA, Gomez-Mouton C, Barber DF, et al. PTEN regulates motility but not directionality during leukocyte chemotaxis. J Cell Sci 2004 117(Pt 25) 6207-6215. 

It seems obvious to assume that by virtue of their powerful regulatory effects of leukocyte recruitment, many chemokine/chemokine receptors may play an important role in an inflammatory disease of the joints such as RA. However, chemokines may have other effects in disease pathogenesis that may not be related to leukocyte chemotaxis. 

Endotoxin activates complement, which then augments the inflammatory response through stimulation of leukocyte chemotaxis, phagocytosis and lysosomal enzyme release, increased platelet adhesion and aggregation, and production of toxic superoxide radicals. 

Mechanisms of Complement Activation. Complement is a major mediator of the inflammatory response. Complement recruits and enlists the participation of humoral and cellular effector systems, induces histamine release from mast cells and directs migration of leukocytes (chemotaxis), in addition to producing phagocytosis and the release of lysosomal constituents from phagocytes. 

NSAID treatment alone. They may be used concurrently with NS AIDS. It mostly takes 1-3 month for their anti-inflammatory action to become apparent. The pharmacodynamics of these antimalarials in RA is uncertain. Possible mechanisms include decreased leukocyte chemotaxis, stabilization of lysosomal membranes, inhibition of DNA and RNA synthesis and trapping of free radicals. 

The effectiveness of chemotherapy is enhanced by adequate immune function however, some antibiotics suppress immune function. For example, tetracychnes can decrease leukocyte chemotaxis and complement activation. Rifampin decreases the number of T lymphocytes and depresses cutaneous hypersensitivity. Antibiotics such as the sulfonamides may induce granulocytopenia or bone marrow aplasia. These effects are not well understood but may be due to enteric bacterial metabohc byproducts of these antibiotics. 

Chloroquine and hydroxychloroquine are used mainly in malaria (see Chapter 52) and in the rheumatic diseases. The mechanism of the antiinflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals. 

Multiple tissue and immunoregulatory activities no similarity of activity is implied by membership of this family Leukocyte chemotaxis and cellular activation... 

Besides 12-LOX in platelets, the 5-LOX isoforms are constitutive in neutrophils. Evidences indicate that LOXs are involved in inflammation diseases and in atherosclerosis. 5-LOX is the enzyme that catalyzes the formation of leukotrienes with potential role for leukocytes and platelets interaction and inflammation. After platelet and leukocyte stimulation, products of both COX-1 and 5-LOX pathways increase. COX-1 activity derivatives increase the vascular permeability mediated by prostaglandins and produce platelet aggregation mediated by TXA2. The product of the lipoxygenase pathway, 5-oxo-6,8,1 1,14-eicosatetraenoic acid (5-Oxo-ETE), induces leukocyte chemotaxis and inflammation. 5-Oxo-ETE is formed by the oxidation of 5S-hydroxy-ETE (5-HETE) by 5-hydroxyeicosanoid dehydrogenase (5-HEDH), a microsomal enzyme found in leukocytes and platelets (42). 

Horwitz, D. A. and Garrett, M. A. (1971). Use of leukocyte chemotaxis in vitro to assay mediators generated by immune reactions. I. Quantitation of mononuclear and polymorphonuclear leukocyte chemotaxis with polycarbonate (nuclepore) filters. J. Immunol. 106, 649-655. 

Faure M, Thivolet J, Gaucherand M. Inhibition of PMN leukocytes chemotaxis by thalidomide. Arch Dermatol Res 1980 269(3) 275-80. 

Tpownson DH, Liptak AE.. Chemokines in the corpus luteum implications of leukocyte chemotaxis. Reprod Biol Endocrinol 2003 1 94. 

Immunological effects of low-fat diets with and without weight loss. J. Am. Coll. Nutr. 22, 174-182. Schmidt, E.B., Pedersen, J.O., Vanning, K., Ernst, E., Jersild, C., Grunnet, N., and Dyerberg, J. 1991. n-3 fatty acids and leukocyte chemotaxis. Effects in hyperlipidemia and dose-response studies in healthy men. Arterioscler. Thromb. 11, 429-435. 

ND, not determined +, stimulatory —, inhibitory 0, none MLCT, mononuclear leukocyte chemotaxis. 

DMARD decreases leukocyte chemotaxis, stabilizes lysosomes, and traps free radicals. Tox GI distress, ototoxicity, myopathy, neuropathy. Other older DMARDs methotrexate, prednisone, sulfasaltizine, gold salts, penicillamine. 

A decrease In leukotrlene 64 formation, an Inducer of Inflammation, and a powerful Inducer of leukocyte chemotaxis and adherence... 

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