Page 50 - Concise Pathology for Exam Preparation ( PDFDrive )

2 Acute and Chronic Inflammation 35

(b) Transmigration across the endothelium (emigration or diapedesis): emigration
is facilitated by focal dissolution of the exposed basement membrane by leukocyte-
derived collagenase
(c) Migration in interstitial tissue towards a chemotactic stimulus (chemotaxis)

Q. What are leukocyte adhesion molecules (LAMs)?
Ans. LAMs are molecules on the leukocytes and endothelial surfaces, which regulate
leukocyte adhesion and transmigration.
• Chemical mediators affect the process of adhesion and transmigration by modulating
the surface expression and avidity of adhesion molecules.
• LAMs are synthesized by endothelial cells and leukocytes.
• LAMs belong to four molecular families—selections, immunoglobulin super family,
integrins and mucin-like glycoproteins.
• There are three types of selectins—L-selectins (expressed on leukocytes); E-selectins
(expressed on endothelial cells) and P-selectins (expressed on platelets and endothe-
lium). The ligands for selectins are sialylated oligosaccharides bound to mucin-like
glycoproteins. TNF and IL1 increase endothelial expression of ligands for integrins like
VCAM-1 (vascular cell adhesion molecule-1) which is the ligand for b1 integrin VLA-4
and ICAM-1 (intercellular adhesion molecule-1) which is the ligand for b2 integrins like
LFA-1 and MAC-1.
• Corticosteroids inhibit adhesion molecule synthesis, thereby decreasing neutrophil
adhesion and increasing the circulating absolute neutrophil count.
• Endotoxins enhance neutrophil adhesion, leading to a reduction in peripheral blood
absolute neutrophil count.
• Endothelial molecule and complimentary leukocyte molecule involved in rolling:

Endothelial molecule (selectins) Complimentary leukocyte molecule for selectins
P-selectin (CD 62P) Sialyl-Lewis X-modified proteins
E-selectin (CD 62E) Sialyl-Lewis X-modified proteins
GlyCam-1 (CD34) L-selectin (CD62L)

• Endothelial molecule and complimentary leukocyte molecule involved in adhesion:
Endothelial molecule (integrins) Complimentary leukocyte molecule for integrins
ICAM-1 (immunoglobulin family) CD 11b/CD18 (b2) integrin (LFA-1, MAC-1)
VCAM-1 (immunoglobulin family) VLA-4 (b1) integrin
GlyCam-1 (CD34) L-selectin (CD62L)

• CD31 or platelet endothelial cell adhesion molecule-1 (PECAM-1) is the molecule involved
in diapedesis.
• There are three main types LAM deficiencies:
• LAM deficiency type 1 (integrin defects which present with recurrent bacterial infec-
tions, usually Staphylococcus aureus and gram-negative enteric bacteria. There is sus-
tained leukocytosis due to the absence of leukocyte margination and the patient gives
a history of delayed umbilical stump separation)
• LAM deficiency type II (selectin defects which manifest with recurrent infections,
Bombay phenotype and mental retardation)
• LAM deficiency type III (mutations in the gene FERMT3 leading to impaired
integrin activation resulting in recurrent infections, leukocytosis and petechial
haemorrhage)

Q. Write briefly on chemotaxis.
Ans. Chemotaxis is defined as a locomotion oriented along a chemical gradient. All
granulocytes, monocytes and to some extent lymphocytes exhibit directed movement to
the area of injury, which is facilitated by chemotactic agents (chemoattractants).

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