A 19-year-old man with leucocyte adhesion deficiency. In vitro and in vivo studies of leucocyte function.
We describe a male patient with leucocyte adhesion molecule deficiency (LAD) of moderate phenotype. Although diagnosis was made only 2 years before his death, the patient survived until 19 years of age. This enabled us to perform a number of novel investigation, both in vivo and in vitro, relating to his leucocyte biology. Monocytes cultured in vitro matured into morphologically normal, phagocytically capable macrophages, which were able to recognize aged 'apoptotic' neutrophils. By injection of radiolabelled autologous neutrophils we demonstrated a prolonged neutrophil half-life, but normal margination, de-margination on exercise, and splenic pooling. Neutrophil adherence in vitro to vascular endothelium was normal. Histological examination of the patient's lungs at post-mortem showed intravascular aggregation of polymorphonuclear leucocytes but a paucity of cells in the interstitium and alveolar spaces. These findings indicate that the peripheral blood leucocytosis commonly observed in these patients may be due to prolonged intravascular neutrophil survival, and suggest that CD11/18 molecules have an important role in facilitating neutrophil emigration from blood vessels at sites of inflammation.
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
K A
KA
Davies
V J
VJ
Toothill
J
J
Savill
N
N
Hotchin
A M
AM
Peters
J D
JD
Pearson
C
C
Haslett
M
M
Burke
S K
SK
Law
N F
NF
Mercer
D000328:Adult; D000943:Antigens, Differentiation / Q000097:blood; D015152:Blotting, Northern; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D018370:Leukocyte-Adhesion Deficiency Syndrome; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D007964:Leukocytosis / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D016028:Receptors, Leukocyte-Adhesion / Q000097:blood; D012883:Skin Ulcer / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology
D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; D012333:RNA, Messenger; D016028:Receptors, Leukocyte-Adhesion; D009240:N-Formylmethionine Leucyl-Phenylalanine