**3. The role of neutrophils**

Neutrophils are the body's first line of innate defense from micro-organismsand and inflam‐ mation. Neutrophils are able to bind to and ingest invading microorganisms such as bacteria, fungi, germs, or any foreign body in the blood by a process known as phagocytosis, most likely due to their defensive and/or phagocytic process is by their ability to release lytic enzymes from their granules and to produce reactive oxygen intermediates (ROI) [2, 3, 4, 8].

Neutrophils cells directly recognize surface-bound or freely secreted molecules produced by bacteria (i.e., pathogen-derived molecules), including peptidoglycan, lipoproteins, lipoteicho‐ ic acid, lipopolysaccharide (LPS), CpG-containing DNA, and flagellin. These pathogenderived molecules, known as pathogen-associated molecular patterns, interact directly with a number of pattern-recognition receptors expressed on the cell surface of neutrophil cell. Pattern-recognition receptors play a role in the recognition of microbes by neutrophils, and the efficiency of phagocytosis by neutrophils is markedly enhanced if microbes are opsonized with serum host proteins, such as complement and/or antibody [9].

Neutrophils have receptors on their surface that help them to contact and bind to tissues and to the vascular endothelium near sites of infection or inflammation [2] and they are the first cells that migrate to the site of invasion or inflammation to start the clearance of infectious particles. In the events of invading foreign threat, they also send warning signals to other innate immune cells [1].

Thus the migration of neutrophils from the blood circulation to surroundings tissues is considered key in triggering host defense.

During the process of migration to site of invasive, neutrophils need to cross the vessel wall (transmigration). This takes place largely at postcapillary venules, where the vessel wall is rather thin, and the diameter of the vessel is sufficiently small that the neutrophils can make contact with the vessel wall, and is yet not occluded by neutrophils when they arrest and make firm contact with the endothelium [6, 9, 10]. Neutrophil transmigration is a highly regulated process that requires the up-regulation of neutrophils and endothelial cell adhesion molecules. During neutrophil adhesion to endothelial cell, binding of neutrophils or endothelial cell adhesion molecules to their ligands may induce intracellular signaling pathways and down‐ stream events, which may in turn modulate neutrophil transmigration. Indeed, the ligation of various adhesion molecules can initiate signal transduction pathways and induce subsequent cellular changes [11, 12].

Moreover, it has been found that neutrophils that migrate through tissues are more effective phagocytic cells than blood neutrophils that is non-migrating neutrophils [6]. Therefore, neutrophils have emerged as key components of the effector and regulatory circuits of the innate and adaptive immune systems, and this has led to a renewed interest in their biology [4]. Recent studies have shown that human neutrophils are a major source of cytokines, which are crucial for the survival, maturation, and differentiation of B cells, and are also involved in bone resorption [4].
