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Dysfunctional LAD-1 neutrophils and colitis

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1 Dysfunctional LAD-1 neutrophils and colitis
Gülbû Uzel, David E. Kleiner, Douglas B. Kuhns, Steven M. Holland  Gastroenterology  Volume 121, Issue 4, Pages (October 2001) DOI: /gast Copyright © 2001 American Gastroenterological Association Terms and Conditions

2 Fig. 1 Flow cytometric evaluation of leukocyte adhesion markers. CD18 (β2 integrin) and CD11a (LFA-1) expression on neutrophils and lymphocytes are shown for both the patient and control. The dotted line represents isotype control. Lymphocyte expression of CD18 is 21.5% and 100% for the patient and control, respectively (A and B). Ninety-nine percent of patient neutrophils express CD18 with a significantly lower GMC (D) than control (C) (20 and 154, respectively). Lymphocyte expression of CD11a (LFA-1) is 21.7% for the patient (F) compared with a 100% expression by the normal (E), while neutrophil expression is 48.5% compared with 100%, (H and G) respectively. Gastroenterology  , DOI: ( /gast ) Copyright © 2001 American Gastroenterological Association Terms and Conditions

3 Fig. 2 (A) Adhesion of neutrophils to plastic (resting and following stimulation with PMA). Low baseline adhesion to plastic for the patient and control was detected. Patient's PMNs were unable to normally up-regulate adhesion following stimulation with PMA. One of 2 studies performed with similar results shown. (B) Staphylococcal killing assay. The patient's PMNs were able to kill 50% fewer staphylococci compared with normal control at 20, 45, and 90 minutes. Control represents bacterial survival in the absence of PMNs. The study shown here was performed with a bacteria:neutrophil ratio of 8:1. One of two studies performed with similar results shown. Gastroenterology  , DOI: ( /gast ) Copyright © 2001 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Endoscopic evaluation of the patient with LAD-1 before surgery. (A) Endoscopic view at the level of the ileocecal valve, showing extensive stricture and ulceration. (B) Punched-out appearance of an ulcer located in the ascending colon; skip areas with normal-appearing mucosa are noted around the ulcerations. Gastroenterology  , DOI: ( /gast ) Copyright © 2001 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Double-contrast barium enema, left lateral decubitis view. Study showing an abnormal terminal ileum and cecum with markedly irregular right colon before surgery. Gastroenterology  , DOI: ( /gast ) Copyright © 2001 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Intestinal resection in a patient with Crohn's disease. (A) A typical ulcer bed in Crohn's disease is shown. The ulcerated surface is covered by a thick neutrophilic exudate, which overlies chronically inflamed granulation tissue. (H&E, 100×). (B) At the point where the regenerating mucosa meets and hangs over the ulcer bed, one can see the dense neutrophilic exudate on the ulcer and a dense lymphoplasmacytic infiltrate beneath the epithelial cells. (H&E, 600×.) Gastroenterology  , DOI: ( /gast ) Copyright © 2001 American Gastroenterological Association Terms and Conditions

7 Fig. 6 Ulcerated colonic mucosa in a patient with LAD-1. (A) In contrast to the ulcer bed in a patient with IBD, the ulcers in the patient with LAD lack a neutrophilic exudate. Instead, the granulation tissue is exposed directly to the bowel lumen. Focally there was heavy colonization of this surface by both fungal and bacterial organisms. (H&E, 100×). (B) Close examination of the granulation tissue shows a relatively sparse lymphoplasmacytic infiltrate in the connective tissue. Dilated blood vessels show neutrophils in the lumen, but almost no neutrophils outside the vessels. (H&E, 400×.) Gastroenterology  , DOI: ( /gast ) Copyright © 2001 American Gastroenterological Association Terms and Conditions


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