A scientist is interested in the mechanisms by which leukocytes traffic to sites of inflammation and infection. She finds that endothelial cells increase the expression of certain cell surface molecules in response to cytokines to allow for leukocyte trafficking. She subsequently creates a knockout mouse that has a deletion in the platelet endothelial cell adhesion molecule 1 (PECAM-1) gene. The protein product of this gene is mainly localized to specific areas on the endothelial cells. Absent expression of this gene will most likely affect which of the following neutrophil functions?

Question

A scientist is interested in the mechanisms by which leukocytes traffic to sites of inflammation and infection.  She finds that endothelial cells increase the expression of certain cell surface molecules in response to cytokines to allow for leukocyte trafficking.  She subsequently creates a knockout mouse that has a deletion in the platelet endothelial cell adhesion molecule 1 (PECAM-1) gene.  The protein product of this gene is mainly localized to specific areas on the endothelial cells.  Absent expression of this gene will most likely affect which of the following neutrophil functions?

Quizplus · Accepted Answer

Inflammation is an important process in the defense against various pathogens. It is characterized by the passage of leukocytes into the inflamed tissue. The following steps are involved in inflammatory leukocyte accumulation: Three leukocyte adhesion deficiency (LAD) syndromes have been identified whereby leukocytes cannot leave the vasculature to migrate into tissues under conditions of inflammation. All are rare, autosomal recessive disorders. LAD type 1 results from the absence of CD18. This leads to the inability to synthesize the beta-2 integrins Mac-1 and LFA1, affecting tight adhesion, crawling, and transmigration. The clinical manifestations include recurrent skin infections without pus formation, delayed detachment of the umbilical cord, and poor wound healing. LAD type 2 is a milder condition, with no delay in the separation of the umbilical cord and less severe and fewer infections. LAD type 3 is similar to type 1 and causes severe, recurrent bacterial infections, delayed separation of the umbilical cord, and bleeding complications (due to affected beta-3 integrins on platelets). Educational objective: Inflammation is characterized by the passage of circulating inflammatory leukocytes into the inflamed tissue. The steps involved include margination, rolling, activation, tight adhesion and crawling, and transmigration. __________ References: Getting to the site of inflammation: the leukocyte adhesion cascade updated. (http://www.ncbi.nlm.nih.gov/pubmed/17717539) Leukocyte adhesion deficiencies: molecular basis, clinical findings, and therapeutic options. (http://www.ncbi.nlm.nih.gov/pubmed/17712991)

A Scientist Is Interested in the Mechanisms by Which Leukocytes