Leukocytes Migrate in Response to Chemical Signals

 Leukocytes can be found throughout the body, migrating from the blood to sites of injury or infection in response to chemical signals, a process referred to as chemotaxis. Migration out of the circulation takes place via diapedesis, an amoeboid mechanism involving the cytoskeleton-mediated contortion of the cell that begins with the extension of a thin pseudopod between the cells of the capillary epithelium (Figure 1). Once the pseudopod becomes anchored on the other side, the contents of the cell are squeezed through the projection by cytoskeletal proteins, filling the distal end of the pseudo pod to form a new, translocated cell body. Once inside the tissues, locomotion proceeds via a similar, stepwise amoeboid mechanism.

Fig1. Diapedesis. Shown, from left to right, are the major steps in diapedesis, the process by which neutrophils and other leukocytes traverse the capillary wall, whose cells are shown in red, in response to chemotactic signals. Cell nuclei are shown in purple and granules in green.

Chemotaxis Is Mediated by G-Protein Coupled Receptors

Leukocytes are attracted to tissues by chemotactic factors such as chemokines, complement fragment C5a, small pep tides derived from bacteria (eg, N-formyl-methionyl-leucyl phenylalanine), and several leukotrienes. These factors bind to one of several cell surface receptors that share similar trans membrane domains comprised of seven membrane-spanning α-helices. Because these receptors all are closely coupled with one or more heterotrimeric guanosine nucleotide-binding proteins (G-proteins), they are often referred to as G-protein coupled receptors. On ligand binding, a signal transduction cascade is initiated in which G-proteins activate phospholipase C, which hydrolyses phosphatidylinositol 4,5-bisphosphate to produce diacylglycerols and the water-soluble second messenger inositol 1,4,5-triphosphate (IP3). The surge in IP3 triggers the release of Ca2+ into the cytoplasm. In neutrophils, the appearance of cytoplasmic Ca2+ activates the components of the actin myosin cytoskeleton responsible for effecting cell migration and granule secretion. Diacylglycerol, together with Ca2+, stimulates protein kinase C and induces its translocation from the cytosol to the plasma membrane, where it catalyzes thephosphorylation of various proteins, including some involved in triggering the respiratory burst (see later).

Chemokines Are Stabilized by Disulfide Bonds

 Chemokines are small, generally 6 to 10 kDa, proteins secreted by activated white blood cells in order to attract additional neutrophils to a site of infection or injury. Chemokines can be divided into four subclasses based on the number and spacing of the cysteine residues that participate in the disulfide bonds that stabilize the protein’s conformation. Type C chemokines are characterized by a single intrachain disulfide bond linking a pair of conserved cysteine residues. In addition to this con served disulfide bond, the other three recognized chemokine groups possess a second disulfide bond (Figure2). In type CC chemokines, one of the additional cysteine residues lies adjacent to the first of the universally conserved residues. In types CXC and CX3 C, these cysteines are separated by one and three intervening amino acid residues, respectively. CX3 C chemokines, the largest of the four types of cytokines, are covalently modified by glycosylation at several sites in their longer C-terminus.

Fig2. Chemokines. This figure depicts the key structural features of type C, CC, CXC, and CX3 C chemokines. The polypeptide chains are depicted in blue with their amino and carboxy termini marked by H2 N and COOH, respectively. Key cysteine residues are denoted as Cys, conserved disulfide bonds at S-S, and spacer amino acids for types CXC and CX3 C using X. Bound carbohydrate is depicted in green.

Integrins Facilitate Diapedesis

The adhesion of leukocytes to vascular endothelial cells is mediated by transmembrane glycoproteins of the integrin and selectin families (see the discussion of selectins in Chapter 46). Integrins consist of noncovalently associated α and β subunits, each of which consists of an extracellular, transmembrane, and intracellular segment. The extracellular segments bind to various extracellular matrix proteins that possess Arg-Gly-Asp sequences, while the intracellular domains bind to cytoskeletal components such as actin and vinculin. Their ability to bridge the exterior and interior of a cell enables integrins to link leukocyte responses (eg, movement and phagocytosis) to changes in the surrounding environment. Some integrins of specific interest with regard to neutrophils are listed in Table 1.

Table1. Principal Integrins of White Blood Cells & Platelets ^a

Type 1 leukocyte adhesion deficiency is caused by the lack of the β2 subunit (also designated CD18) of LFA-1 and of two related integrins found in neutrophils and macrophages, Mac-1 (CD11b/CD18) and p150,95 (CD11c/CD18). This impairs the ability of the affected leukocytes to adhere to vascular endothelial cells, impeding diapedesis. Fewer white blood cells enter their infected tissues; thereby lowering the resistance of the affected individuals to bacterial and fungal infections.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم صناعة الشبابيك يباشر أعمال إدامة شباك مقام الإمام المهدي (عجّل الله فرجه)

المجمَع العلمي ينظم ندوته القرآنية الأسبوعية في جامعة الكوفة

جامعة العميد تقيم الملتقى العلمي الثاني لخريجي كلية طب الأسنان

ضمن دورتها العلمية (في رحاب العقيدة) الهيأة العليا لإحياء التراث تقدم محاضرة عن مفهوم الأسبقية في الإسلام

المزيد

الآخبار الصحية

اللحظات الأخيرة قبل الموت.. هذا هو تسلسل "فقدان الحواس"

وخز الأطراف وضعف الذاكرة.. علامات على نقص فيتامين هام

عادة صباحية بسيطة.. تأثيرها قد يحسن ضغط الدم

عادات يومية تدمر قلبك بصمت.. خبراء يطلقون التحذير

المزيد

الآخبار التكنلوجية

الذكاء الاصطناعي يفك لغز آثار أقدام الديناصورات

القمر أولا.."سبيس إكس" تؤجل خططها الخاصة بالرحلات إلى المريخ

الذكور أم الإناث؟ دراسة "تنسف الشائع" بشأن التوحد

خبير يكشف عن اقتراب العلماء من فك شفرات "لغات الحيوانات" !

المزيد

مواضيع ذات صلة

Phagocytic Leukocytes Generate Reactive Oxygen Species During the Respiratory Burst

Platelets

The Biochemical Basis of The ABO System

The Red Blood Cell Membrane

Oxidation of Heme Iron Compromises oxygen Transport

Hypervariable Regions Confer Binding Specificity

Immunoglobulins Are Comprised of Multiple Polypeptide Chains

Serum Inhibitors Prevent Indiscriminate Proteolysis

Intracellular Iron Homeostasis is Tightly Regulated

Clinical Biochemistry of Exercise: Biochemical Adaptation

Iron is Strictly Conserved

Haptoglobin Protects the Kidneys