Circulating endothelial precursor

The existence of circulating endothelial precursor (CEP) cells in adults has been reported (60-62), It has also been demonstrated that similar precursor cells may give rise to both ECs and perivascular mural cells (63). Furthermore, in an in vitro model of angiogenesis, normal vascular development has been shown to require the presence of the CD45+/c-Kit+/CD34+ hematopoietic stem cells (64), which are similar and may be related to adult CEP cells. 

Rafii S. Circulating endothelial precursors Mystery, reality, and promise. J Clin Invest 2000 105 17-19. 

Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S. Expression of VEGFR-2 and ACl 33 by circulating human CD34(-I-) cells identifies a population of functional endothelial precursors. Blood 2000 95 952-958. 

Peichev, M., Naiyer, A.J., Pereira, D., et al. Expression of VEGFR-2 and AC133 by circulating human CD34-1- cells identifies a population of functioned endothelial precursors. Blood 95,952-958 (2000)... 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

Fibrinolysis refers to the process of fibrin digestion by the fibrin-specific protease, plasmin. The fibrinolytic system is similar to the coagulation system in that the precursor form of the serine protease plasmin circulates in an inactive form as plasminogen. In response to injury, endothelial cells synthesize and release tissue plasminogen activator (t-PA), which converts plasminogen to plasmin (Figure 34-3). Plasmin remodels the thrombus and limits its extension by proteolytic digestion of fibrin. 

Early studies suggested that IL-1 and TNF were chemotactic for PMN. However, it has become apparent that this activity resides in a family of molecules of 10 kDa, called neutrophil activating peptides (NAP) or IL-8 (L15). IL-1 and TNF induce the release of these molecules from mononuclear cells, fibroblasts, endothelial cells, and keratinocytes and they act on a specific receptor expressed by PMN. The main activity ascribed to these molecules is PMN chemotaxis, but the molecules may cause oxygen radical and enzyme release by PMN and mobilize PMN into the circulation. The common feature that identifies members of this family of peptides is alignment of four cysteine residues. IL-8 is the most potent chemotactic member of this family. Synthesized as a 99-amino-acid precursor, lL-8 is released as a 79-amino-acid molecule, IL-8a, which itself is further cleaved to 77- and 72-amino-acid forms, IL-8P and IL-8y. IL-8y is predominantly found to be associated with macrophages and may reflect the proteolytic enzymes released by macrophages. Receptors for IL-8 have been identified on PMN and approximately 20% of lymphocytes. The three-dimensional structure of IL-8 (NAP-1) has been reported (C27). 

ACE is present on the luminal face of vascular endothelial cells throughout the circulation, and circulating renin of renal origin can be sequestered by the arterial wall and other tissues, permitting the local conversion of precursors to Angll. Indeed, rrumy vascular beds locally produce Angl and 11. 

Patients with leukemia experience a variety of hemorrhagic (bleeding) manifestations caused by a decreased number of platelets. Platelets are small cells that initiate clot formation at the site of endothelial injury. Because of the uncontrolled proliferation of white cells within the limited space of the marrow, the normal platelet precursor cells (the megakaryocytes) in the marrow are "squeezed" or crowded and fail to develop into mature platelets. Consequently, the number of mature platelets (thrombocytes) in the circulation falls, and a thrombocytopenia develops. Because there are fewer platelets to contribute to clot formation, bleeding problems are common. 

While the typical cells in Gaucher s disease are usually limited to a few organs, NPC may be found almost everywhere in the body. However, corresponding to the distribution of the reticulo-endothelial system they will be most abundant in tissues of this system which therefore should preferably be biopsied for diagnostic purposes. As a rule, NPC cannot be recovered from circulating blood, and, according to Bloom (1928), the vascular endothelium is not a precursor for these cells. 

Eosinophil precursors originate in the bone marrow, where they divide and further differentiate into mature eosinophils, which shortly circulate in the bloodstream, and get recruited into target tissues such as the lung through cell attraction and adhesion to the endothelial cells (through adhesion molecules), diapedesis, and chemotaxis within tissues. Eosinophil recruitment to tissues... 

Only the free form of the fatty acid precursors of eicosanoids can be utilized by the enzymes for conversion to the biologically active metabolites. However, the amount of precursor free fatty acid in the cytoplasm and circulating is usually low and so too is basal eicosanoid formation. Eurthermore, basal eicosanoid formation may depend on dietary and adipose tissue fatty acid composition. The amount of eicosanoid precursor free fatty acids is controlled to a large extent by incorporation and release from cellular phospholipids. Which eicosanoids are produced during stimulated synthesis may depend on membrane fatty acid composition as well as the cell type involved. Dietary fatty acid composition, therefore, has the potential to effect basal and stimulated synthesis of eicosanoids and influence endothelial function and thrombotic and inflammatory responses. 

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