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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}} {{Alison}}
|QuestionAuthor= {{Rim}} (Reviewed by  {{YD}} and  {{AJL}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Immunology
|MainCategory=Immunology
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|MainCategory=Immunology
|MainCategory=Immunology
|SubCategory=General Principles
|SubCategory=General Principles
|MainCategory=Immunology
|MainCategory=Immunology
|MainCategory=Immunology
|MainCategory=Immunology
|MainCategory=Immunology
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|MainCategory=Immunology
|MainCategory=Immunology
|SubCategory=General Principles
|SubCategory=General Principles
|Prompt=Neutrophils are critically involved in the process of inflammation. The sequence of events in the recruitment of neutrophils from the vessel lumen to the extracellular matrix, referred to as extravasation, and can be divided up into four steps. Which of the following signaling mediators is involved in the migration of the neutrophils across the endothelial cells?
|Prompt=Neutrophils are critically involved in the process of inflammation. The sequence of events in the recruitment of neutrophils from the vessel lumen to the stromal compartment is called extravasation, which can be divided into four major steps. Which of the following signaling mediators is involved in the migration of neutrophils across endothelial cells?
|Explanation=The involvement of polymorphonuclear neutrophils (PMN) in inflamted tissue involves a series of interactions that are collectively known as extravasation. PMNs within the endothelium are first activated and flattened by weak adhesive interactions that before they are allowed to emigrate across the endothelium. Prior to activation, PMNs first undergo rolling, which is a saltatory movement of PMN along the endothelium, to locate inflammatory mediators. PMNs are then activated by local inflammatory mediators. Activation allows PMNs to acquire strong adhesive interactions with the endothelium. Following adhesion, PMNs are believed to travel mostly in a paracellular fashion and exit blood vessels in a process called diapedesis. Finally, PMNs are guided by chemotactic agents and travel through the interstitium to the site of inflammation.


|Explanation= [[PECAM-1]] is involved in diapedesis, which is the migration of the neutrophils across the endothelial cells.
In order to achieve all steps of extravasation, PMNs utilize proteins that are expressed on either the vascular endothelial cells or on the PMNs themselves:
The four steps of [[extravasation]] are:
# Margination and rolling: mainly e-selectin, p-selectin, GlyCAM-1, and CD34 expressed on vascular endothelium, and Sialyl-Lewis and L-selectin expressed on PMN.
# Margination and rolling
# Tight-binding: mainly ICAM-1 (CD54) expressed on vascular endothelium, and CD11/18 integrins, LFA-1, MAC-1, and VLA-4 integrin expressed on PMN.
# Tight-binding
# Diapedsis: mainly PECAM-1 (CD31) expressed on both vascular endothelium and PMN
# Diapedsis is the migration of the neutrophils across the endothelial cells.
# Migration: mainly C5a, IL-8, LTB4, kallikrein, and platelet-activating factor expressed on vascular endothelium.
# Migration is the movement of neutrophils through the interstitium to the location of the infection, guided by C5a, IL-8, kallikrein, and platelet-activation factors, the signalling mediators.
|AnswerA=E-selectin and P-selectin
 
|AnswerAExp=[[E-selectin]] and P-selectin are mainly involved in the rolling phase of extravasation.
|EducationalObjectives= [[Inflammation]] involves several steps including the rolling phase of the [[neutrophils]], their binding to the [[endothelium]], [[diapedesis]], and migration to the site of inflammation.  [[PECAM 1]] is involved in diapedesis, which is the migration of the leukocytes across the endothelial cells.
|AnswerB=ICAM-1
|AnswerA=E selectin and P selectin
|AnswerBExp=[[ICAM-1]] (CD54) is mainly involved in the tight binding (adhesion) of [[neutrophils]] to the [[endothelium]].
|AnswerAExp=[[E selectin]] and P selectin are involved in the rolling phase.
|AnswerC=PECAM-1
|AnswerB=ICAM 1
|AnswerCExp=[[PECAM-1]] (CD31) is mainly involved in diapedesis, which is the migration of the neutrophils across the endothelial cells.
|AnswerBExp=[[ICAM-1]] is involved in the tight binding of [[neutrophils]] to the [[endothelium]].
|AnswerC=PECAM 1
|AnswerCExp=[[PECAM-1]] is involved in diapedesis, which is the migration of the neutrophils across the endothelial cells.
|AnswerD=C5a
|AnswerD=C5a
|AnswerDExp=[[C5]] a is involved in the migration of leykocytes through the interstitum towards the site of inflammation.
|AnswerDExp=[[C5]]a is mainly involved in the migration of leykocytes through the interstitum towards the site of inflammation.
|AnswerE=Interleukin 8
|AnswerE=IL-8
|AnswerEExp=[[Interleukin]] 8 is involved in the migration of [[leukocytes]] through the interstitium towards the site of [[inflammation]].
|AnswerEExp=IL-8 is mainly involved in the migration of [[leukocytes]] through the interstitium towards the site of [[inflammation]].
 
|EducationalObjectives=[[PECAM-1]] is mainly involved in diapedesis, which is the migration of the leukocytes across endothelial cells during the process of PMN extravasation.
|References= First Aid 2014 page 224
|References=Scalia R, Lefer AM. In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature. J Leukoc Biol. 1998;64(2):163-9.<br>
First Aid 2014 page 224
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=Inflammation, Diapedesis, Leukocyte, Leukocyte adhesion, Endothelium, Endothelial cell
|WBRKeyword=Inflammation, Diapedesis, Leukocyte, Leukocyte adhesion, Endothelium, Endothelial cell, PECAM-1, CD31
|Approved= Yes
|Approved=Yes
}}
}}

Latest revision as of 23:27, 27 October 2020
Author [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2])]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Immunology
Sub Category SubCategory::General Principles
Prompt [[Prompt::Neutrophils are critically involved in the process of inflammation. The sequence of events in the recruitment of neutrophils from the vessel lumen to the stromal compartment is called extravasation, which can be divided into four major steps. Which of the following signaling mediators is involved in the migration of neutrophils across endothelial cells?]]
Answer A AnswerA::E-selectin and P-selectin
Answer A Explanation [[AnswerAExp::E-selectin and P-selectin are mainly involved in the rolling phase of extravasation.]]
Answer B AnswerB::ICAM-1
Answer B Explanation [[AnswerBExp::ICAM-1 (CD54) is mainly involved in the tight binding (adhesion) of neutrophils to the endothelium.]]
Answer C AnswerC::PECAM-1
Answer C Explanation [[AnswerCExp::PECAM-1 (CD31) is mainly involved in diapedesis, which is the migration of the neutrophils across the endothelial cells.]]
Answer D AnswerD::C5a
Answer D Explanation [[AnswerDExp::C5a is mainly involved in the migration of leykocytes through the interstitum towards the site of inflammation.]]
Answer E AnswerE::IL-8
Answer E Explanation [[AnswerEExp::IL-8 is mainly involved in the migration of leukocytes through the interstitium towards the site of inflammation.]]
Right Answer RightAnswer::C
Explanation [[Explanation::The involvement of polymorphonuclear neutrophils (PMN) in inflamted tissue involves a series of interactions that are collectively known as extravasation. PMNs within the endothelium are first activated and flattened by weak adhesive interactions that before they are allowed to emigrate across the endothelium. Prior to activation, PMNs first undergo rolling, which is a saltatory movement of PMN along the endothelium, to locate inflammatory mediators. PMNs are then activated by local inflammatory mediators. Activation allows PMNs to acquire strong adhesive interactions with the endothelium. Following adhesion, PMNs are believed to travel mostly in a paracellular fashion and exit blood vessels in a process called diapedesis. Finally, PMNs are guided by chemotactic agents and travel through the interstitium to the site of inflammation.

In order to achieve all steps of extravasation, PMNs utilize proteins that are expressed on either the vascular endothelial cells or on the PMNs themselves:

  1. Margination and rolling: mainly e-selectin, p-selectin, GlyCAM-1, and CD34 expressed on vascular endothelium, and Sialyl-Lewis and L-selectin expressed on PMN.
  2. Tight-binding: mainly ICAM-1 (CD54) expressed on vascular endothelium, and CD11/18 integrins, LFA-1, MAC-1, and VLA-4 integrin expressed on PMN.
  3. Diapedsis: mainly PECAM-1 (CD31) expressed on both vascular endothelium and PMN
  4. Migration: mainly C5a, IL-8, LTB4, kallikrein, and platelet-activating factor expressed on vascular endothelium.

Educational Objective: PECAM-1 is mainly involved in diapedesis, which is the migration of the leukocytes across endothelial cells during the process of PMN extravasation.
References: Scalia R, Lefer AM. In vivo regulation of PECAM-1 activity during acute endothelial dysfunction in the rat mesenteric microvasculature. J Leukoc Biol. 1998;64(2):163-9.
First Aid 2014 page 224]]

Approved Approved::Yes
Keyword WBRKeyword::Inflammation, WBRKeyword::Diapedesis, WBRKeyword::Leukocyte, WBRKeyword::Leukocyte adhesion, WBRKeyword::Endothelium, WBRKeyword::Endothelial cell, WBRKeyword::PECAM-1, WBRKeyword::CD31
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