Basophils, proliferation

IL-9 is a T-celi growth factor that acts in synergy with other cytokines (with IL-2, it causes proliferation of T cells and with IL-4, it promotes IgE and IgG synthesis by plasma-cytes). However, it supports the growth of some Th2 T-cell clones in the absence of IL-2 or IL-4. It has also been found to enhance the proliferative action of IL-3 on mast ceE progenitors, to augment basophil proliferation and ery-throid colony formation, and to stimulate the proliferation of megakaryoblastic leukemia... 

T-celi proliferation Basophil proliferation Erythroid precursor proliferation... 

Increase red blood cell mass and granulocyte proliferation Decrease lymphocyte, monocyte, and basophil proliferation... 

Although mast cells and basophils probably account for >90% of stored histamine in the body, histamine is also present in platelets, enterochromaffin-like cells, endothelial cells, and neurons. Histamine can act as a neurotransmitter in the brain. Histaminergic nerves have their cell bodies within a very small area of the brain (the magnocellular nuclei of the posterior hypothalamus) but have axons in most areas of the forebrain. There is also evidence for axons projecting into the spinal (Fig. 1) cord. Finally, there is evidence that histamine synthesis can be induced in tissues undergoing rapid tissue growth and repair. In certain neonatal tissues (e.g. liver), the rate of synthesis of this unstored diffusable histamine (termed nascent histamine) is profound and may point to a role for histamine is cell proliferation. 

In spite of the above-mentioned similarities between basophils and mast cells, they differ in many other aspects [1,2]. Basophils complete their differentiation within the bone marrow, and mature basophils circulate in the peripheral blood and do not usually infiltrate into peripheral tissues unless inflammation takes place. Mast cells originate from hematopoietic cells in the bone marrow as do basophils, but they mature in peripheral tissues after their bone marrow-derived precursors enter the circulation and migrate into peripheral tissues. Mature mast cells reside in peripheral tissues and do not usually circulate in the peripheral blood. The lifespan of basophils is very short (several days), in contrast to that of mast cells (weeks to months). Basophils do not proliferate once they terminally differentiate whereas mature mast cells keep potential to expand in response to various stimuli. These differences between basophils and mast cells, including distinct anatomical localization, suggest their differential roles in vivo. 

In addition to its effects on haematopoietic cells, GM-CSF can also affect the function of mature cells. GM-CSF treatment increases the survival, cytotoxicity and eicosanoid formation by eosinophils, and can increase the tu-mouricidal activity, cytokine expression, surface antigen expression and oxidative metabolism of macrophages. It is chemotactic for endothelial cells, can induce the proliferation of some tumour cells, stimulates histamine release from basophils and affects the viability and function of Langerhans cells. Its effects on mature neutrophils are described in 7.2.1, 7.3.4. 

In group I, the following were observed megakaryocyte size reduction, basophilic cytoplasm, reduced and hyperchromic nuclei which are signs of suppressed proliferation. In group II, the cell and nuclei are big with a distinct nucleolus showing increased proliferative activity of the lymphoid tissue (Fig. 11). 

B. IL-2 stimulates the immune system by binding to the IL-2 receptors on responsive immune cells, causing differentiation and proliferation of T helper and T cytotoxic cells. It has no direct effect on the HIV virus, complement, or basophils. 

Evidence indicates that steroids affect other cells and substances that modulate inflammation. Exposure of human basophils to steroid in culture inhibits histamine release induced by an IgE-dependent stimulus. Steroids inhibit phospholipase A2, which prevents biosynthesis of arachidonic acid and subsequent formation of prostacyclin, thromboxane A, prostaglandins, and leukotrienes. Steroids also decrease capillary permeability and fibroblast proliferation and the quantity of collagen deposition, thereby influencing tissue regeneration and repair. 

Dysplasia This condition is defined as variably large, differentshaped hepatocytes, mostly in locahzed groups, with enlarged, pleomorphic and hyperchromatic nuclei as well as enlarged nucleoli. These dysplastic hepatocytes may often be polyploid. Dysplasia can occur as a macrocellular (with eosinophilic cytoplasm) or microcellular (with basophilic cytoplasm and increased proliferation) variant. The latter is considered to be a precancerous stage. Dysplastic foci with a diameter of l(-2) mm consist of enriched, predominantly small-cellular dysplastic hepatocytes. Dysplastic nodes with a diameter of 0.3-1.0 cm contain an atypical architecture and cellular atypias trabecular or pseudo-glandular structures are evident. Atypical hepatocytes are often clear-cellular, basophilic or steatotic. Fluent transition into HCC is seen occasionally. (87, 95)... 

Interleukin-3 is prodnced by activated T lymphocytes and stimnlates the proliferation and differentiation of the grannlocyte, macrophage, eosinophil, basophil, erythroid, megakaryocyte, and mast cell hneages (1). 

Enhances survival, proliferation and differentiation of multipotential stem cells and committed precursors of the granulocyte, macrophage, erythroid, eosinophil, neutrophil, megakaryocyte, mast cell and basophil lineages Enhances effector functions of myeloid end cells such as phagocytosis and cytotoxicity... 

Promotes chemotaxis and granule release by neutrophils, basophils, T cells Mitogenic for myeloid cells, supports antigen-independent growth of helper T cells Inhibits interferon secretion, induces thymocyte proliferation in presence of other IL s, inhibits Thl cytokine production Induction of synthesis of acute phase proteins, enhances stimulation of hematopoietic cell proliferation by IL-3 and T-cell development of B cells Activates NK cells, stimulates production of IFN-a by Thl cells... 

A basic understanding of normal hematopoiesis is needed before one can understand the pathogenesis of leukemia. The reader is referred to Chap. 98 for a detailed discussion of hematopoiesis. Normal hematopoiesis consists of multiple well-orchestrated steps of cellular development. A pool of pluripotent stem cells undergoes differentiation, proliferation, and maturation, to form the mature blood cells seen in the peripheral circulation. These pluripotent stem cells initially differentiate to form two distinct stem cell pools. The myeloid stem cell gives rise to six types of blood cells (erythrocytes, platelets, monocytes, basophils, neutrophils, and eosinophils), while the lymphoid stem cell differentiates to form circulating B and T lymphocytes. Leukemia may develop at any stage and within any cell line. 

Marsman, D. S., and Popp, J. A. (1994). Biological potential of basophilic hepatocellular fod and hepatic adenoma induced by the peroxisome proliferator, Wy-14,643. Carcinogenesis 15, 111-117. 

Chemokines are a superfamily of small proteins which play a crucial role in immune and inflammatory reactions and in viral infection (Hedrick and Zlotnik, 1996 Baggi-olini et al, 1997 Rollins, 1997). Most chemokines cause migration of leukocytes, but these molecules also affect angiogenesis, proliferation of hematopoietic precursors, and viral responses. Based on a cysteine motif, a CXC, CC, C and CX3C family have been identified (Fig. 1). CXC (or a) chemokines are active on neutrophils and lymphocytes while CC (or (3) chemokines exert their action on multiple leukocyte subtypes, including monocytes, basophils, eosinophils, T-lymphocytes, dendritic cells (DC) and NK cells, but they are generally inactive on PMN. Eotaxins... 

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