Leukocytes adhesion

Mechanisms of Leukocyte Adsorption. The exact mechanism of leukocyte adhesion to filter media is not yet fuUy understood. Multiple mechanisms simultaneously contribute to the adhesion of cells to biomaterials, however, physical and biological mechanisms have been distinguished. Physical mechanisms include barrier phenomenon, surface tension, and electrostatic charge biological mechanisms include cell activation and cell to cell binding. 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

Many low weight compounds produced by microor-ganism-like formylated peptides as well as endogenous mediators are chemotactic for leukocytes and promote the inflammatory process. The main endogenous compounds are listed in Table 1 and are derived from activated plasma protein cascades that function as amplification mechanisms, are performed and released from activated cells or are de novo synthesized on demand by cells participating in or being affected by inflammatory events. The major modulators of leukocyte adhesion to endothelial cells are listed in Table 2. 

Inflammation. Table 2 Modulation of leukocyte adhesion to endothelial cells... 

Leukocyte adhesion deficiency, type II (MIM 266265) Probably mutations affecting a Golgi-located GDP-fucose transporter, resulting in defective fucosylation. 

CD11a/CD18,CDllb/CD18, CDllc/CD18 j Adhesion molecules (members of the 1 integrin family) Deficient in leukocyte adhesion deficiency type 1 (MIM 116920)... 

Koch, A.E., Burrows, J.C., Haines, G.K., Carlos, T.M. and Harlan, J.M. (1991). Immunolocalisation of endothelial and leukocyte adhesion molecules in human rheumatoid and osteoarthritic synovial tissues. Lab. Invest. 64, 313-320. 

Perry, M.A. and Granger, D.N. (1992). Leukocyte adhesion in local versus hemorrhage-induced ischemia. Am. J. Physiol. 163, H810-H815. 

Johnston B, Butcher EC. Chemokines in rapid leukocyte adhesion triggering and migration. Semin Immunol 2002 14(2) 83-92. 

Kuziel WA, Morgan SJ, Dawson TC, et al. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc Natl Acad Sci U S A 1997 94(22) 12053-12058. 

Although ICAM-1 seems not to be involved in the sickle cell adhesion to vascular endothelium, it may exacerbate vasoocclusion by promoting leukocyte adhesion. In this context, it is remarkable to note that in HU-treated SCA patients, the strongest correlation was found between total white cell count and severity of crisis rather than with erythrocyte-related parameters [28]. The current consensus is that leukocyte endothelium adhesion may initiate vasoocclusion followed by RBC sequestration and entrapment in the microvascular lumen with ensuing painful crisis. Thus overexpression of ICAM-1 is expected to promote VOC. The data... 

Kusterer K, Bojunga J, Enghofer M, Heidenthal E, Usadel KH, Kolb H, Martin S. Soluble ICAM-1 reduces leukocyte adhesion to vascular endothelium in ischemia-reperfusion injury in mice. Am J Physiol 1998 275 G377-380. 

Y. van Kooyk and C. G. Figdor, Avidity regulation of integrins The driving force in leukocyte adhesion, Curr. Opin. Cell Biol., 12 (2000) 542-547. 

Tegoulia VA, Cooper SL (2000) Leukocyte adhesion on model surfaces under flow effects of surface chemistry, protein adsorption, and shear rate. J Biomed Mater Res 50 291-301... 

Morigi M, Micheletti G, Figliuzzi M, Imberti B, Karmali MA, Remuzzi A, Remuzzi G, Zoja C Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood 1995 86 4553-4558. 

In the recent review Carr et al. [54] considered potential antiatherogenic mechanisms of a-tocopherol and ascorbic acid. These authors concluded that these antioxidants are able to inhibit LDL oxidation, leukocyte adhesion to the endothelium, and vascular endothelial dysfunction. They also believe that ascorbic acid is more effective than a-tocopherol in the inhibition of these pathophysiological processes due to its capacity of reacting with a wide spectrum of oxygen and nitrogen free radicals and its ability to regenerate a-tocopherol. 

This is a rare, inherited disorder characterised by recurrent and, often, life-threatening infections. This dysfunction results from absent or very low expression of the glycoprotein family, LFA-1, CR3 and gp 150,95, which function in leukocyte adhesion ( 3.9). These adhesion molecules are normally responsible for various functions, such as the following ... 

Note IL-1 = interleukin-1 GM-CSF = granulocyte-marcophage colony-simulating factor PDGF = platelet-derived growth factor TGF-)5 = transforming growth factor-) ICAM = intercellular leukocytic adhesion molecule ELAM = extracellular leukocytic adhesion molecule. 

Forlow SB, Schurr JR, Rolls JK, Bagby GJ, Schwarzenberger PO, Ley K Increased granulopoiesis through interleukin-17 and granulocyte colony-stimulating factor in leukocyte adhesion molecule-deficient mice. Blood 2001 98 3309-3314. 

Inoue T, Sakai Y, Morooka S, Hayashi T, Takayanagi K, Takabatake Y. Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1996 28 1127-1133. 

Hallahan D, Kuchibhotla J, Wyble C. Cell adhesion molecules mediate radiation-induced leukocyte adhesion to the vascular endothelium. Cancer Res 1996 56 5150-5155. 

Leukocyte Adhesion Deficiency Type 2. Patients with this condition have a defect in the transport or production of the carrier molecule for the carbohydrate L-fucose (guanosine disphosphate L-fucose). The lack of fucose affects the ability of neutrophils to interact with ligands on endothelial cells such as P-selectins and E-selectins (81). Patients are susceptible to recurrent infections similar to those afflicting patients with type 1 leukocyte adhesion deficiency, have periodontal problems, and, in addition, may exhibit growth retardation and neurologic defects. Treatment with oral fucose has been known to be effective in reducing the frequency of infections (80). 

Leukocyte adhesion deficiency type 1 Patients are exposed to recurrent infections and teeth problems such as periodontitis. 

Leukocyte adhesion deficiency type 2 Same cUnical problems as in type 1. In addition, patients have growth retardation and neurologic defects. Treatment wifii oral fucose reduces frequency of infections. 

Marquardt, T, Brune, T, Luhn, K., etal., Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism. J. Pediatr. 134, 681-688 (1999). 

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