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Expression of the CD11/CD18, leukocyte adhesion molecule 1, and CD44 adhesion molecules during normal myeloid and
G S Kansas1, M J Muirhead, M O Dailey
1Department of Pathology, University of Iowa College of Medicine, Iowa City.
Insights
This study maps adhesion molecule expression during human myeloid and erythroid cell development. Key molecules like CD44, LFA-1, and LAM-1 help define distinct stages of monocyte, neutrophil, and erythrocyte differentiation.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Adhesion molecules play crucial roles in cell-cell interactions and trafficking.
- Understanding their expression patterns during hematopoietic differentiation is vital for deciphering developmental pathways.
Purpose of the Study:
- To investigate the expression patterns of CD11/CD18, CD44, and leukocyte adhesion molecule 1 (LAM-1) during human myeloid and erythroid differentiation.
- To phenotypically define discrete stages of monocyte, neutrophil, and erythrocyte development using flow cytometry.
Main Methods:
- Three-color flow cytometry was employed to analyze adhesion molecule expression.
- Cells were identified and categorized based on the expression of specific surface markers including CD11/CD18 family members, CD44, LAM-1, CD33, CD15, CD11c, CD11b, CD14, lymphoid antigens, glycophorin, CD71, and CD45.
Main Results:
- Distinct expression profiles for CD44, LFA-1, and LAM-1 were identified across different stages of myeloid (monocyte, granulocyte) and erythroid differentiation.
- Early myeloid progenitors (CD33loCD15-) showed high CD44 expression with variable LFA-1 and LAM-1 levels.
- Monocyte commitment was marked by CD33 upregulation and specific CD11a/CD18 expression, while granulocyte development involved CD15 upregulation and CD33/CD44 downregulation.
- Erythroid precursors (CD44hi, LFA-1lo, LAM-1+) lost LFA-1 and LAM-1 before glycophorin expression, with CD44 levels varying in later stages.
Conclusions:
- The study successfully phenotypically defined sequential stages of normal human monocyte, neutrophil, and erythrocyte development.
- The expression of LFA-1, LAM-1, and high CD44 levels on primitive hematopoietic cells suggests their critical involvement in leukocyte adhesion during development.
Abstract:
We have used three-color flow cytometry to investigate the pattern of expression of the CD11/CD18, CD44, and leukocyte adhesion molecule 1 (LAM-1) adhesion molecules during myeloid and erythroid differentiation in humans. The earliest myeloid cells, identified as CD33loCD15-, were exclusively CD44hi but contained both leukocyte function-associated antigen 1 (LFA-1hi) and LFA-1lo cells, as well as LAM-1+ and LAM-1- cells. This CD33loCD15- myeloid subpopulation expressed only low levels of CD11c and failed to express CD11b, CD14, or any lymphoid (CD3, CD16, CD19) antigens or glycophorin. Commitment to monocyte differentiation, suggested by the presence of an LFA-1hi CD11c+ subset within the CD33loCD15- subpopulation, was clearly signaled by upregulation of CD33; these monocyte-lineage committed cells were exclusively CD33hi, CD44hi, CD11ahi, CD11c+, and exhibited a broad range of intensity of CD15 expression. Later stages of monopoiesis were identified by acquisition of CD11b, and subsequently of CD14. Myeloid cells committed to granulopoiesis remained LFA-1lo, and underwent a sharp upregulation of CD15 along with downregulation of both CD33 and CD44. Successive stages of granulocyte development were marked by expression of CD11b and, subsequently, of CD16. The earliest cells capable of erythroid differentiation were CD44hi, LFA-1lo, and LAM-1+. Both LFA-1 and LAM-1 were lost before the onset of glycophorin (glyco) expression, whereas CD44 expression remained high on glyco+ cells, which also expressed CD45. CD44 expression was intermediate on glyco+ CD71+ cells, and low on glyco+ CD45- CD71- cells, similar to normal, circulating erythrocytes. Our results allow us to phenotypically define discrete stages in the normal development of monocytes, neutrophils, and erythrocytes. The expression of LFA-1, LAM-1, and high levels of CD44 on the most primitive hematopoietic cells detectable by flow cytometry suggests that at least some of these molecules are critically involved in leukocyte adhesion during development.